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Monthly Update Report for Trials Started in March 2026


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1: Summary data from new trials identified for Leukemia and Lymphoma.


Overview

Number of Trials: 21

These 21 trials investigate treatments for hematologic malignancies including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, myelodysplastic syndromes (MDS), myeloproliferative neoplasms, and Hodgkin/non-Hodgkin lymphomas. Interventions include novel BTK inhibitors (pirtobrutinib, tirabrutinib), BCL-2 inhibitors (venetoclax), menin inhibitors (olutasidenib, bleximenib), CAR T-cell therapies (CD30, CD64, CD83), bispecific antibodies (mosunetuzumab, polatuzumab vedotin, blinatumomab), hypomethylating agents (azacitidine, decitabine), and combination chemotherapy regimens. Several trials target relapsed/refractory disease, while others focus on newly diagnosed patients, elderly populations, or pediatric survivors. Supportive care and lifestyle interventions addressing insomnia, weight management, and exercise are also included.

Common Criteria Across Trials

Common Inclusion

  • Age ≥18 years (adult trials)
  • Confirmed diagnosis of specific hematologic malignancy
  • Measurable disease by imaging or laboratory assessment
  • ECOG/Karnofsky performance status 0-2
  • Adequate organ function (renal, hepatic, cardiac, pulmonary)
  • Adequate bone marrow function (ANC, platelets, hemoglobin thresholds)
  • Life expectancy >12 weeks or >3 months
  • Negative pregnancy test for women of childbearing potential
  • Agreement to use effective contraception
  • Ability to provide informed consent
  • Recovery from prior therapy toxicities

Common Exclusion

  • Pregnant or breastfeeding
  • Active uncontrolled infection
  • Known HIV with detectable viral load or low CD4 count
  • Active hepatitis B or C infection
  • CNS involvement by malignancy (symptomatic)
  • Prior allogeneic transplant with active GVHD or recent transplant (<60-180 days)
  • Concurrent active malignancy requiring treatment
  • Significant cardiovascular disease (NYHA Class III/IV, recent MI)
  • Major surgery within 2-4 weeks
  • Use of strong CYP3A inhibitors/inducers
  • Uncontrolled autoimmune disease
  • Systemic corticosteroids above specified doses
  • QTc prolongation >470-480 msec
  • Known hypersensitivity to study drugs

Outcomes Summary

Primary Outcomes

Secondary Outcomes


2: Extracted Trials with New Information


Trials with Special Criteria

Genomic / Biomarker Trials

Unique or Unusual Criteria

Trials with Emerging Treatments


3: Individual Trial Overviews


NCT07428707

Immune Profiling of CLL/SLL Treated With First-Line Pirtobrutinib

Organization/Sponsor: National Institutes of Health Clinical Center (CC)


Example patient: A 62-year-old treatment-naive patient with CLL presenting with progressive lymphadenopathy (2.5 cm cervical nodes), lymphocytosis of 45,000 B cells/μL, ECOG status 1, adequate organ function, and no cardiovascular disease or active infections.

Phase N/A

Interventions

  • Drug: Pirtobrutinib
    Summary: Orally available, selective, non-covalent Bruton's tyrosine kinase (BTK) inhibitor that reversibly blocks BTK signaling and B-cell receptor pathway activation. FDA-approved for relapsed/refractory mantle cell lymphoma and CLL/SLL after prior BTK inhibitor therapy; this trial evaluates first-line use. Sources: FDA label, NCI Thesaurus.

Key Inclusion

  • Age ≥18 years
  • Confirmed diagnosis of CLL or SLL per iwCLL guidelines with CD5, CD19, CD20, CD23 coexpression
  • Previously untreated CLL with ≥1 lymph node amenable to core-needle biopsy
  • Active disease requiring treatment per iwCLL guidelines
  • Measurable disease: lymphadenopathy ≥1.5 cm, splenomegaly >13 cm, lymphocytosis ≥5,000 B cells/μL, or bone marrow infiltration ≥30%
  • ECOG performance status 0-2
  • Adequate organ function: creatinine clearance ≥30 mL/min, hemoglobin ≥8 g/dL, ANC ≥0.75×10⁹/L, platelets ≥50×10⁹/L
  • Adequate coagulation: aPTT/PTT and PT/INR ≤1.5× ULN

Key Exclusion

  • Richter Transformation or documented CNS involvement
  • Active hepatitis B (HBsAg positive or HBV DNA positive) or hepatitis C (HCV RNA positive)
  • HIV positive with detectable viral load and/or CD4 count <350
  • Stroke or intracranial hemorrhage within 6 months
  • Active cardiovascular disease: unstable angina, MI within 3 months, LVEF ≤40%, QTcF >470 msec, NYHA Class 3-4 heart failure
  • Therapeutic anticoagulation with warfarin or vitamin K antagonists
  • Chronic systemic steroid therapy >20 mg prednisone daily or immunosuppressive therapy within 7 days
  • Active uncontrolled autoimmune cytopenia requiring new or escalated therapy within 4 weeks

NCT06956781

Optimizing Behavioral Health Services Following Pediatric Trauma Exposure

Organization/Sponsor: University of Rochester


Example patient: A 12-year-old child with PTSD from physical assault, living with a non-offending grandmother for six months, not currently in trauma therapy, with stable mood medication for three months.

Phase N/A

Interventions

  • Behavioral: Psychological Placebo
    Summary: An inactive control treatment providing baseline measurements through placebo effects and supportive care, aiming to reduce anxiety without active ingredients (NCI Thesaurus, Web Search).
  • Behavioral: Bi-lateral Stimulation
    Summary: A therapeutic intervention involving alternating sensory stimulation, commonly used in trauma-focused therapies to facilitate processing of traumatic memories (Web Search).
  • Behavioral: Cognitive Processing
    Summary: Cognitive Processing Therapy restructures negative thought patterns and maladaptive beliefs to improve mental health and coping strategies in trauma-exposed individuals (Web Search).
  • Behavioral: Exposure
    Summary: Exposure therapy involves systematic confrontation with trauma-related memories or stimuli to reduce avoidance and distress responses (NCI Thesaurus, Web Search).
  • Behavioral: Emotion Regulation
    Summary: A psychological intervention employing cognitive and behavioral strategies to enhance coping skills, emotional awareness, and management of stress and anxiety (Web Search).

Key Inclusion

  • Child ages 8-17 exposed to at least one DSM-defined trauma
  • Meets PTSD diagnostic criteria from identified trauma
  • Stable caregiving environment for two months
  • Psychotropic medications stable for two months if applicable
  • Caregiver or child has smartphone for app download

Key Exclusion

  • Suicidal ideation with intent or current psychotic disorder
  • Intelligence quotient below 70
  • Currently receiving behavioral health intervention for PTSD or trauma
  • Caregiver is perpetrator of identified trauma
  • MRI contraindicators such as metal in body

NCT07444268

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of DSP-5336 Following a Single Oral Dose in Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Myeloproliferative Neoplasms

Organization/Sponsor: Sumitomo Pharma America, Inc.


Example patient: A 52-year-old male with relapsed acute myeloid leukemia after two prior therapies, ECOG status 1, adequate organ function, and no recent stem cell transplant or radiolabeled study participation.

Phase 1

Interventions

  • Drug: [14C]-DSP-5336
    Summary: Radiolabeled form of DSP-5336 used to study absorption, metabolism, and excretion in patients with leukemia and other hematologic malignancies (Web Search).
  • Drug: DSP-5336
    Summary: Orally bioavailable menin inhibitor (enzomenib) that blocks menin-MLL complex formation, reducing downstream gene expression and inhibiting proliferation of MLL-rearranged leukemic cells (NCI Thesaurus).

Key Inclusion

  • Age ≥18 years
  • Advanced hematological malignancy that is relapsed, refractory, or progressed after standard treatments
  • Prior toxicities resolved to ≤Grade 1 (except ≤Grade 2 alopecia or neuropathy)
  • Adequate kidney and liver function
  • ECOG performance status ≤2
  • Able to attend required study visits including confinement period
  • Female patients surgically sterile or postmenopausal
  • Male patients permanently sterile or agree to contraception

Key Exclusion

  • Acute promyelocytic leukemia
  • QTcF >480 msec or history of torsades de pointes
  • Left ventricular ejection fraction ≤45%
  • Gastrointestinal surgery or conditions affecting oral drug absorption
  • HSCT, CAR-T, or modified T-cell therapy within 60 days
  • Active GVHD requiring medical intervention beyond topical steroids
  • Anticancer drugs or investigational treatment within 14 days or 5 half-lives
  • Exposure to >2 radiolabeled drug studies in last 12 months

NCT07224100

Phase II Study of Dose-Adjusted EPOCH ± Rituximab + Ponatinib for Adults With Newly-Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia/Lymphoma Genomic-based

Organization/Sponsor: University of Washington


Example patient: A 45-year-old man with newly-diagnosed Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia confirmed by FISH showing BCR::ABL1 translocation, ECOG performance status 1, with no prior ALL therapy and adequate organ function.

Phase II

Interventions

  • Procedure: Positron Emission Tomography
    Summary: PET uses radioactive tracers like FDG to visualize metabolic activity in tissues, detecting cancer and evaluating treatment response (NCI Thesaurus, Web Search).
  • Procedure: Computed Tomography
    Summary: CT scans use X-rays to create cross-sectional images for detecting cancer spread and monitoring tumor progression (NCI Thesaurus, Web Search).
  • Procedure: Bone Marrow Biopsy
    Summary: Removal of bone marrow tissue containing bone spicules and hematopoietic elements to diagnose leukemia, lymphoma, and evaluate disease progression (NCI Thesaurus).
  • Procedure: Bone Marrow Aspiration
    Summary: Aspiration of immature hematopoietic elements from bone marrow to evaluate hematopoietic disorders and detect abnormal cells in leukemia and lymphoma (NCI Thesaurus).
  • Procedure: Biospecimen Collection
    Summary: Collection of tissue and fluid samples for testing, research, and analysis of genetic and molecular features in cancer (NCI Thesaurus, Web Search).
  • Drug: Vincristine
    Summary: Vinca alkaloid that disrupts microtubule formation during cell division, arresting tumor cells in metaphase; used for acute leukemia and lymphomas (FDA label, NCI Thesaurus).
  • Drug: Rituximab
    Summary: Chimeric monoclonal antibody targeting CD20 antigen on B cells, inducing cytolytic mechanisms to deplete B cells; indicated for CD20-positive B-cell malignancies including NHL and CLL (FDA label, NCI Thesaurus).
  • Drug: Prednisone
    Summary: Synthetic glucocorticoid that suppresses immune and inflammatory responses by activating nuclear receptors and inhibiting proinflammatory cytokines; used in leukemia and lymphoma combination therapies (FDA label, NCI Thesaurus).
  • Drug: Ponatinib
    Summary: Multitargeted tyrosine kinase inhibitor that inhibits all forms of BCR-ABL including T315I mutation; indicated for Ph+ ALL and CML resistant to prior kinase inhibitors (FDA label, NCI Thesaurus).
  • Drug: Pegfilgrastim
    Summary: Pegylated recombinant G-CSF that stimulates neutrophil production from bone marrow to reduce chemotherapy-induced neutropenia and infection risk (FDA label, Web Search).
  • Drug: Filgrastim
    Summary: Recombinant G-CSF that stimulates production and release of neutrophils from bone marrow to prevent severe neutropenia in chemotherapy patients (FDA label, Web Search).
  • Drug: Etoposide
    Summary: Topoisomerase II inhibitor that prevents DNA ligation after strand breaks, inhibiting replication and transcription; used for refractory testicular tumors and small cell lung cancer (FDA label, NCI Thesaurus).
  • Drug: Doxorubicin
    Summary: Anthracycline antibiotic that intercalates DNA, inhibits topoisomerase II, and generates free radicals; indicated for leukemias, lymphomas, breast cancer, and other solid tumors (FDA label, NCI Thesaurus).
  • Drug: Cyclophosphamide
    Summary: Alkylating agent that cross-links DNA to disrupt replication; indicated for lymphomas, leukemias, multiple myeloma, and solid tumors (FDA label, NCI Thesaurus).

Key Inclusion

  • Adults age 18 years and older with newly-diagnosed Ph+ B-ALL
  • BCR::ABL1 translocation confirmed by cytogenetics, FISH, or RT-PCR
  • Marrow or blood involvement by abnormal lymphoblasts detectable by flow cytometry
  • Total bilirubin ≤1.5x ULN (≤4x ULN for Gilbert's disease, ≤5x ULN for hepatic ALL involvement)
  • AST/ALT ≤2.5x ULN (≤8x ULN for hepatic ALL involvement)
  • Creatinine clearance >30 ml/min/1.73m² by MDRD equation
  • ECOG performance status 0-2 (3 allowed if due to ALL)
  • Anticipated survival at least 3 months independent of ALL

Key Exclusion

  • Burkitt lymphoma/leukemia
  • Prior systemic therapy for ALL except symptom control or hyperleukocytosis management
  • Isolated extramedullary or known parenchymal CNS disease
  • Acute pancreatitis within 1 year or known chronic pancreatitis
  • Symptomatic atherosclerotic cardiovascular disease within 1 year
  • Active resistant hypertension requiring 3+ antihypertensive medications
  • Venous thromboembolic event within 6 months
  • Hypersensitivity or intolerance to any study agents

NCT06871410

CD83 CAR T in Relapsed or Refractory Acute Myeloid Leukemia (AML): A Phase I Trial

Organization/Sponsor: Roswell Park Cancer Institute


Example patient: A 52-year-old with relapsed AML after two prior therapies, Karnofsky score 80%, adequate organ function, and an identified potential allogeneic transplant donor.

Phase I

Interventions

  • Procedure: Questionnaire Administration
    Summary: Patient self-reported outcome assessment to measure quality of life and treatment effects; no direct biological mechanism (NCI Thesaurus, Web Search).
  • Diagnostic Test: Positron Emission Tomography
    Summary: Imaging using radioactive tracers to visualize metabolic activity, evaluate treatment response, and detect metastatic disease (NCI Thesaurus, Web Search).
  • Procedure: Lumbar Puncture
    Summary: Invasive procedure to collect cerebrospinal fluid for diagnostic testing of central nervous system involvement in leukemia (NCI Thesaurus, Web Search).
  • Procedure: Leukapheresis
    Summary: Blood filtration procedure to collect white blood cells for CAR T-cell therapy manufacturing (NCI Thesaurus, Web Search).
  • Drug: Hydroxyurea
    Summary: Antimetabolite that inhibits ribonucleotide reductase to reduce DNA synthesis; used to control white blood cell counts in chronic myeloid leukemia (FDA label, NCI Thesaurus).
  • Drug: Fludarabine Phosphate
    Summary: Fluorinated nucleoside analog that inhibits DNA synthesis via fludarabine triphosphate; used for lymphodepletion chemotherapy prior to CAR T infusion (FDA label, NCI Thesaurus).
  • Diagnostic Test: Echocardiography
    Summary: Ultrasound imaging to visualize heart structures and assess cardiac function; used to monitor left ventricular ejection fraction (NCI Thesaurus).
  • Drug: Cyclophosphamide
    Summary: Alkylating agent that cross-links DNA to disrupt cancer cell replication; used for lymphodepletion chemotherapy prior to CAR T infusion (FDA label, NCI Thesaurus).
  • Diagnostic Test: Computed Tomography
    Summary: X-ray imaging to create cross-sectional body scans; used to monitor tumor progression and treatment response (NCI Thesaurus, Web Search).
  • Diagnostic Test: Chest Radiography
    Summary: Imaging to visualize chest organs and detect leukemia involvement in lungs or mediastinum (Web Search).
  • Procedure: Biospecimen Collection
    Summary: Gathering tissue and fluid samples for research to analyze genetic and molecular features of cancer (NCI Thesaurus, Web Search).
  • Biological: Autologous Anti-CD83 CAR T-cells
    Summary: Engineered T-cells with chimeric antigen receptor targeting CD83-expressing AML cells; investigational cell therapy for relapsed/refractory AML (Web Search).

Key Inclusion

  • Age ≥18 years old
  • Relapsed or refractory AML based upon ELN 2022 criteria
  • Karnofsky performance status ≥70%
  • Creatinine clearance ≥40 mL/min
  • Left ventricular ejection fraction >45%
  • Absolute lymphocyte count ≥0.2 x 10^9/L
  • Life expectancy ≥12 weeks
  • Preliminarily eligible for allogeneic hematopoietic cell transplantation

Key Exclusion

  • Acute promyelocytic leukemia (APL; AML M3)
  • Active central nervous system leukemia
  • Systemic glucocorticoid >10 mg daily prednisone equivalent within 4 weeks of CAR T infusion
  • HIV seropositivity or active hepatitis B or C infection
  • Active grade II-IV acute GVHD requiring treatment
  • Prior solid organ transplant
  • Active autoimmune disease requiring immunosuppressive therapy
  • Other active malignancy within 2 years

NCT07218341

Long-Term Safety of Pirtobrutinib in Participants From Study LOXO-BTK-20020 With BTKi Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Organization/Sponsor: Eli Lilly and Company


Example patient: A 68-year-old patient with chronic lymphocytic leukemia previously treated with BTK inhibitors, currently enrolled in the parent study LOXO-BTK-20020 and transitioning to long-term safety follow-up.

Phase N/A

Interventions

  • Drug: Pirtobrutinib
    Summary: Pirtobrutinib is an orally available, selective, non-covalent Bruton's tyrosine kinase (BTK) inhibitor that reversibly blocks BTK signaling and BCR pathway activation, inhibiting growth of malignant B-cells. FDA-approved for relapsed/refractory CLL/SLL and mantle cell lymphoma after prior BTK and BCL-2 inhibitor therapy, with effectiveness in BTK inhibitor-resistant cases including C481 mutations (FDA label, NCI Thesaurus).
  • Drug: Idelalisib
    Summary: Idelalisib is an orally bioavailable PI3K-delta inhibitor that blocks phosphatidylinositol-3,4,5-trisphosphate production, inhibiting tumor cell proliferation and survival in hematopoietic malignancies. FDA-approved for relapsed CLL in combination with rituximab in patients with comorbidities, not recommended for first-line treatment (FDA label, NCI Thesaurus).

Key Inclusion

  • Actively participating in study J2N-MC-JZNN/LOXO-BTK-20020

Key Exclusion

  • Not applicable to this study

NCT07388563

A Phase I Trial of Azacitidine and Abatacept in Relapsed or Refractory T-Cell Lymphoma

Organization/Sponsor: National Institutes of Health Clinical Center (CC)


Example patient: A 52-year-old with relapsed peripheral T-cell lymphoma after initial chemotherapy, ECOG status 1, adequate organ function, and no active infections or CNS involvement.

Phase 1

Interventions

  • Biological: Abatacept
    Summary: A recombinant fusion protein combining CTLA-4 and IgG1 domains that blocks T-cell costimulation by binding CD80/CD86 on antigen-presenting cells, preventing CD28 interaction and modulating immune response; FDA-approved for rheumatoid arthritis and graft-versus-host disease prophylaxis (FDA label, NCI Thesaurus).
  • Drug: Azacitidine
    Summary: A pyrimidine nucleoside analogue that reversibly inhibits DNA methyltransferase causing hypomethylation and reactivation of tumor suppressor genes; also disrupts RNA function; FDA-approved for myelodysplastic syndromes and studied in lymphomas (FDA label, NCI Thesaurus).

Key Inclusion

  • Histologically confirmed T-cell lymphoma (PTCL-NOS, AITL, TFH, ALCL, EATL, MEITL, ATLL, or other TCL)
  • Relapsed or refractory disease after initial systemic treatment
  • Age ≥18 years
  • ECOG performance status ≤2
  • ANC ≥1,000 cells/mcL or ≥500 if bone marrow involvement
  • Platelets ≥50,000 cells/mcL or ≥25,000 if bone marrow involvement
  • Adequate renal function (creatinine ≤2 mg/dL or GFR ≥40 mL/min/1.73 m²)
  • Adequate hepatic function (bilirubin ≤1.5x ULN, AST/ALT ≤3x ULN)

Key Exclusion

  • Second malignancy requiring active systemic therapy
  • Latent tuberculosis infection
  • Active systemic infection requiring anti-infective treatment within 1 day
  • Anti-cancer therapy within 2 weeks prior to study initiation
  • Known allergy or hypersensitivity to study drugs
  • Pregnancy
  • Active central nervous system involvement with lymphoma
  • Hepatitis B surface antigen (HBsAg) positive

NCT07071155

A Pilot Study of Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia (M-HArbOr) Genomic-based

Organization/Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins


Example patient: A 62-year-old man with chronic myelomonocytic leukemia, ECOG 1, spleen 7 cm below costal margin, platelets 40,000/microL, no prior JAK inhibitor therapy, and adequate organ function.

Phase N/A

Interventions

  • Drug: Azacitidine
    Summary: Azacitidine is a pyrimidine nucleoside analogue that inhibits DNA methyltransferase, reactivating tumor suppressor genes and disrupting RNA function. It is indicated for myelodysplastic syndromes and acute myeloid leukemia. Sources: FDA label, NCI Thesaurus.
  • Drug: Momelotinib
    Summary: Momelotinib is an oral JAK1/2 and ACVR1 inhibitor that blocks JAK-STAT signaling and reduces hepcidin, increasing red blood cell production. It is indicated for intermediate or high-risk myelofibrosis with anemia. Sources: FDA label, NCI Thesaurus.

Key Inclusion

  • Age 18 or older with MDS/MPN or CNL by WHO or ICC criteria
  • Chronic phase disease with <10% blasts in peripheral blood and marrow
  • ECOG Performance Score 0-2
  • Baseline splenomegaly ≥5 cm below costal margin or ≥450 cm3 on imaging
  • Platelets ≥25,000/microL, ANC ≥0.75 x 10^9/L without transfusion or growth factor support
  • Creatinine clearance ≥30 mL/min, total bilirubin ≤1.5×ULN
  • Life expectancy >24 weeks
  • Willing to use effective contraception during treatment and follow-up

Key Exclusion

  • MDS/MPN with SF3B1 mutation and thrombocytosis
  • Peripheral blood or marrow blast percentage >10%
  • Prior lack of response to momelotinib or hypomethylating agents
  • AST or ALT above 2.5 x ULN (or 5 x ULN if liver involved by extramedullary hematopoiesis)
  • Prior momelotinib treatment at any time
  • Active invasive concurrent malignancy interfering with safety or efficacy assessment
  • Chronic active or acute viral hepatitis A, B, or C infection
  • Pregnant or breastfeeding

NCT07294677

CApivasertib, Venetoclax And Low-intensity chemotheRapY for Adults With ALL/LBL

Organization/Sponsor: University of Chicago


Example patient: A 52-year-old adult with relapsed B-cell ALL showing 15% blasts in bone marrow, ECOG status 1, controlled diabetes on oral agents, no active infections, and adequate organ function.

Phase N/A

Interventions

  • Chemotherapy Regimen: mini-hyperCVD
    Summary: Mini-hyperCVD combines cyclophosphamide, vincristine, and dexamethasone with inotuzumab ozogamicin and blinatumomab to treat relapsed B-cell ALL by inducing apoptosis and preventing cell division (Web Search).
  • Drug: Nelarabine
    Summary: Nelarabine is a nucleoside metabolic inhibitor that incorporates into DNA to inhibit synthesis and induce S-phase apoptosis in tumor cells (FDA label, NCI Thesaurus).
  • Biological: Blinatumomab
    Summary: Blinatumomab is a bispecific CD19/CD3 T-cell engager that brings T-cells and CD19-positive B-cells together to induce cytotoxic killing in ALL (FDA label, NCI Thesaurus).
  • Biological: Rituximab
    Summary: Rituximab is a chimeric anti-CD20 monoclonal antibody that depletes B-cells through CD20-directed cytolytic mechanisms for treating B-cell malignancies and autoimmune conditions (FDA label, NCI Thesaurus).
  • Drug: Venetoclax
    Summary: Venetoclax is a BCL-2 inhibitor that binds BCL-2 protein to restore apoptosis in cancer cells, used for CLL, SLL, and AML (FDA label, NCI Thesaurus).
  • Drug: Capivasertib
    Summary: Capivasertib is an oral AKT kinase inhibitor that blocks PI3K/AKT/mTOR signaling to inhibit cancer cell growth, survival, and metabolism (FDA label, NCI Thesaurus).

Key Inclusion

  • Relapsed or refractory acute lymphoid leukemia (B-ALL, T-ALL, ETP-ALL, mixed phenotype) or lymphoblastic lymphoma
  • Previously untreated ALL/LBL (Cohort 3 only)
  • ≥5% leukemic blasts in bone marrow or peripheral blood (Cohorts 1-2), ≥20% (Cohort 3)
  • Age ≥18 years (Cohorts 1-2), ≥40 years (Cohort 3)
  • ECOG performance status 0-2
  • Adequate organ function per protocol
  • At least 2 weeks from major surgery or radiation
  • Effective contraception required during and after treatment

Key Exclusion

  • Ph-positive ALL or Burkitt's leukemia/lymphoma
  • Pregnant or breastfeeding
  • Uncontrolled infection, hepatitis B/C, or HIV
  • Symptomatic CNS disease or spinal cord compression
  • Concurrent active malignancy requiring treatment
  • Uncontrolled cardiac disease or diabetes mellitus (type 1 or insulin-dependent)
  • Cannot discontinue strong CYP3A inducers or grapefruit products
  • Prior systemic chemotherapy for ALL/LBL (Cohort 3 only, except steroids ≤2 weeks, hydroxyurea, ATRA, intrathecal therapy)

NCT06782542

Single-Arm Phase 2 Study of Olutasidenib, Venetoclax, and Azacitidine in IDH1 Mutated Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Eligible for Intensive Induction Chemotherapy Genomic-based

Organization/Sponsor: University of Miami


Example patient: A 62-year-old male with newly diagnosed secondary AML with IDH1 R132 mutation arising from prior MDS treated with hypomethylating agents, ECOG performance status 1, adequate organ function, and no FLT3-ITD mutation.

Phase 2

Interventions

  • Drug: Azacitidine
    Summary: Azacitidine is a nucleoside metabolic inhibitor that inhibits DNA methylation, reactivating tumor suppressor genes silenced by hypermethylation. It is indicated for myelodysplastic syndromes and acute myeloid leukemia, disrupting abnormal cell proliferation in bone marrow disorders (FDA label, NCI Thesaurus).
  • Drug: Venetoclax
    Summary: Venetoclax is a selective BCL-2 inhibitor that induces apoptosis in cancer cells by binding to BCL-2 protein and restoring apoptotic processes. It is indicated for CLL, SLL, and newly diagnosed AML in combination with hypomethylating agents (FDA label, NCI Thesaurus).
  • Drug: Olutasidenib
    Summary: Olutasidenib is an IDH1 inhibitor that targets mutated isocitrate dehydrogenase-1 enzyme, specifically used to treat acute myeloid leukemia with IDH1 R132 mutations to improve patient outcomes (Summary of Web Search).

Key Inclusion

  • Adults aged 18-75 years eligible for intensive induction chemotherapy
  • ECOG performance status ≤2
  • Newly diagnosed AML with IDH1 R132 mutation confirmed locally
  • Secondary AML including prior hypomethylating agent exposure for MDS, MPN, or MDS/MPN allowed
  • Adequate organ function: AST/ALT ≤3×ULN, bilirubin ≤2×ULN, creatinine clearance ≥30 mL/min
  • Recovery from prior treatment toxicity to Grade ≤1
  • QTcF ≤480 msec
  • Negative pregnancy test for women of childbearing potential

Key Exclusion

  • Relapsed or refractory AML
  • ELN 2022 favorable risk AML except NPM1 mutated
  • Acute promyelocytic leukemia
  • Positive FLT3-ITD mutation
  • Active CNS involvement by leukemia
  • Prior therapy with olutasidenib, ivosidenib, other IDH1 inhibitors, venetoclax, or BCL-2 inhibitors
  • Strong CYP3A inhibitors or inducers within 7-14 days prior to first dose
  • Active hepatitis B, hepatitis C, or HIV with detectable viral load

NCT06594939

Multicenter Phase II Study of Mosunetuzumab and Polatuzumab Vedotin With Split-Dose CHP Chemotherapy for Elderly Patients With Diffuse Large B-Cell Lymphoma

Organization/Sponsor: Medical College of Wisconsin


Example patient: A 72-year-old patient with newly diagnosed CD20-positive diffuse large B-cell lymphoma Stage IV, ECOG 1, LVEF 55%, no prior anthracycline exposure, creatinine clearance 50 mL/min, and vaccinated for COVID-19.

Phase II

Interventions

  • BLA: Pegfilgrastim
    Summary: Recombinant granulocyte colony-stimulating factor that stimulates bone marrow to produce neutrophils, used to prevent chemotherapy-induced neutropenia in cancer patients (FDA label, NCI Thesaurus).
  • ANDA: Prednisone
    Summary: Synthetic glucocorticoid that binds nuclear receptors to suppress immune and inflammatory responses, induces lymphocyte apoptosis, used in combination chemotherapy for lymphomas (FDA label, NCI Thesaurus).
  • ANDA: Doxorubicin
    Summary: Anthracycline antibiotic that intercalates DNA and inhibits topoisomerase II, preventing DNA replication and generating free radicals, used for lymphomas and leukemias (FDA label, NCI Thesaurus).
  • ANDA: Cyclophosphamide
    Summary: Alkylating agent that cross-links DNA to disrupt cancer cell replication, indicated for lymphomas, leukemias, and solid tumors (FDA label, NCI Thesaurus).
  • BLA: Mosunetuzumab
    Summary: Bispecific antibody binding CD20 on B-cells and CD3 on T-cells to redirect cytotoxic T-lymphocytes against CD20-expressing lymphoma cells, approved for relapsed/refractory follicular lymphoma (FDA label, NCI Thesaurus).
  • BLA: Polatuzumab Vedotin
    Summary: Antibody-drug conjugate targeting CD79b on B-cell lymphomas, delivering cytotoxic agent to destroy cancer cells, used for diffuse large B-cell lymphoma (Web Search).

Key Inclusion

  • Newly diagnosed, untreated, CD20 positive diffuse large B-cell lymphoma
  • Ann Arbor Stage II bulky, III, or IV disease
  • Measurable disease by PET/CT using Lugano criteria (lymph node >1.5 cm)
  • Left ventricular ejection fraction ≥50%
  • Karnofsky Performance Score ≥50 or ECOG 0-2
  • Patients aged 70-74 who are unfit/frail by CIRS-G score
  • Adequate biospecimen sample for Adaptive Clonality ID Test
  • At least one dose of COVID-19 vaccine

Key Exclusion

  • Prior treatment for DLBCL with chemotherapy, immunotherapy, or biologic therapy
  • CNS or meningeal involvement at diagnosis
  • Primary mediastinal large B cell lymphoma
  • Richter's Transformation from chronic lymphocytic leukemia
  • History of previous anthracycline exposure
  • Creatinine clearance <40 mL/min
  • Current Grade >1 peripheral neuropathy
  • On immunosuppressant therapy for active autoimmune disease

NCT05544968

A Phase I Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of Anti-CD30 Bispecific Antibody-Armed Anti-CD3-Activated Autologous T-Cells (CD30 biAb-AATC) in Patients With Relapsed/Refractory CD30 Positive Hematopoietic Malignancies

Organization/Sponsor: Medical College of Wisconsin


Example patient: A 45-year-old male with relapsed Hodgkin lymphoma after three prior therapies, CD30 expression 25% by immunohistochemistry, measurable 2 cm cervical lymphadenopathy, Karnofsky score 70%, and adequate organ function.

Phase 1

Interventions

  • Biological: anti-CD30 Bispecific Antibody-armed anti-CD3-Activated Autologous T-cells (CD30 biAb-AATC)
    Summary: Bispecific antibody-armed autologous T-cells targeting CD30 on malignant cells and CD3 on T-cells to enhance T-cell cytotoxicity against CD30-positive hematopoietic malignancies; investigational therapy being tested for safety and efficacy (Web Search).
  • Biological: GM-CSF
    Summary: Recombinant human GM-CSF that stimulates production and function of granulocytes and macrophages to accelerate myeloid recovery, reduce infection risk, and enhance immune function post-chemotherapy or transplantation (FDA label, NCI Thesaurus).

Key Inclusion

  • CD30-positive hematopoietic malignancies including Hodgkin lymphoma, non-Hodgkin lymphoma, AML, or ALL
  • Second or greater recurrence or refractory to at least 2 prior therapeutic regimens for HD, NHL, and ALL
  • First or greater relapse or primary refractory AML with at least 1 prior induction attempt
  • CD30 surface expression ≥20% on leukemia blasts or ≥1% on lymphoma cells by flow cytometry or immunohistochemistry
  • Measurable disease for lymphomas (nodal ≥1.5 cm or extranodal ≥1.0 cm) or relapsed/refractory disease for leukemias
  • Age ≥18 years with Karnofsky performance status ≥50%
  • Adequate organ function including creatinine ≤1.5x ULN, ALT <3x ULN, LVEF ≥40%, and oxygen saturation >90% on room air
  • Recovery from prior therapy toxicities to ≤Grade 2

Key Exclusion

  • HSCT or CAR T-cell therapy within 60 days or evidence of veno-occlusive disease post-transplant
  • Grade >3 toxicities from prior treatment per CTCAE v5.0
  • Chronic systemic steroid or immunosuppressive therapy within 7 days
  • Uncontrolled systemic fungal, bacterial, viral, or other infection
  • HIV-positive patients on antiretroviral therapy
  • Prior anti-CD30 therapy-related pulmonary toxicity or progressive multifocal leukoencephalopathy
  • NYHA Class III or IV heart failure, ventricular arrhythmias, or uncontrolled hypertension
  • Pregnant or breastfeeding females or second malignancy within 1 year except in situ cancer or skin basal/squamous cell carcinoma

NCT07292272

Halt Aging in Survivors of Blood Cancers: the HALTAging-1 Study

Organization/Sponsor: University of Nebraska


Example patient: A 62-year-old patient with chronic lymphocytic leukemia on maintenance therapy, no cardiac or neurological conditions, and able to safely participate in aerobic exercise.

Phase N/A

Interventions

  • Behavioral: Virtual Gym Membership
    Summary: Virtual gym membership promoting physical activity through exercise and social support to improve physical health and well-being in blood cancer patients (Summary of Web Search).
  • Behavioral: Supervised Exercise and Coaching
    Summary: Supervised exercise program with coaching to improve physical function, reduce inflammation, enhance immune response, and reduce treatment side effects in leukemia and lymphoma patients (Summary of Web Search).

Key Inclusion

  • Age ≥50 years
  • History of hematological malignancy
  • Able to give informed consent

Key Exclusion

  • Receiving intensive induction or consolidation chemotherapy
  • Neurodegenerative disease, stroke, or uncontrolled psychotic disorders in past 3 months
  • Decompensated heart failure, unstable angina, or disorders limiting aerobic exercise
  • Cardiopulmonary test results precluding safe exercise
  • Life expectancy less than 6 months
  • Not planning follow-up at participating center

NCT07191119

Feasibility and Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia

Organization/Sponsor: St. Jude Children's Research Hospital


Example patient: A 32-year-old English-speaking childhood ALL survivor with persistent insomnia (ISI score 10) who has home Wi-Fi access and no cardiac or neurological contraindications.

Phase N/A

Interventions

  • Device: Soterix tVNS device
    Summary: Transcutaneous auricular vagus nerve stimulation device that modulates the nervous system via ear stimulation to treat insomnia in childhood ALL survivors (Summary of Web Search).
  • Device: Soterix tVNS device (sham programmed)
    Summary: Sham control device mimicking tVNS procedure without active investigational components for comparison (NCI Thesaurus).
  • Outcome Measure: Neurocognitive and mental health outcomes
    Summary: Assessment of cognitive deficits from chemotherapy and cranial radiation impacting memory, attention, and executive function in childhood leukemia survivors (Summary of Web Search).
  • Outcome Measure: Sleep Quality
    Summary: Assessment of individual sleep quality (NCI Thesaurus).

Key Inclusion

  • Survivor of Acute Lymphoblastic Leukemia (ALL)
  • Enrolled on SJLIFE
  • Age 20-50 years at enrollment
  • Insomnia Severity Index >=8
  • Access to home Wi-Fi and Smartphone
  • Able to speak and understand English
  • Diagnosed before age 21 years

Key Exclusion

  • Pregnant or planning pregnancy
  • Implanted electrical medical devices (pacemaker)
  • Taking stimulants or seizure medications
  • History of skin irritation during inner ear stimulation
  • Currently using technological sleep intervention (e.g. CPAP)
  • History of syncope, cardiac dysrhythmia, vascular disease, or coronary artery disease (CTCAE >2)
  • Active cranial nerve disorder, neuropathy, neuralgia, or stroke (CTCAE >2)
  • Seizures in past year

NCT07468916

Ropeginterferon Alfa-2b for MDS/MPN Overlap Syndromes, Including CMML and MDS/MPN-RS-T

Organization/Sponsor: Jonsson Comprehensive Cancer Center


Example patient: A 62-year-old male with CMML diagnosed per WHO 2022 criteria, 8% marrow blasts, platelet count 75,000/uL, ANC 1,500/uL, ECOG PS 1, no prior interferon or azacitidine therapy, and no history of depression or autoimmune disease.

Phase N/A

Interventions

  • Drug: Ropeginterferon Alfa-2B
    Summary: N-terminal pegylated interferon alfa-2b that activates immune responses to suppress abnormal blood cell production, FDA-approved for polycythemia vera, administered subcutaneously (FDA label).
  • Procedure: Questionnaire Administration
    Summary: Patient self-reported outcome assessment to measure quality of life and treatment effects (NCI Thesaurus).
  • Procedure: Computed Tomography
    Summary: Imaging using X-rays to construct cross-sectional scans for monitoring disease progression and treatment effectiveness (NCI Thesaurus).
  • Procedure: Bone Marrow Biopsy
    Summary: Removal of bone marrow core tissue for microscopic analysis to diagnose and evaluate hematopoietic disorders including MDS/MPN (NCI Thesaurus).
  • Procedure: Bone Marrow Aspiration
    Summary: Needle aspiration of bone marrow to collect immature hematopoietic elements for evaluation of hematopoietic disorders and cytogenetic studies (NCI Thesaurus).
  • Procedure: Biospecimen Collection
    Summary: Gathering tissue and fluid samples for testing and research to analyze genetic and molecular features (NCI Thesaurus).

Key Inclusion

  • Age ≥18 years
  • MDS/MPN overlap syndrome per WHO 2022 classification including CMML, MDS/MPN with neutrophilia, MDS/MPN-RS-T, or MDS/MPN NOS
  • Blast ≤10% by marrow immunohistochemistry
  • Platelet count >50,000/uL
  • ANC >1000/uL
  • ECOG performance status ≤2
  • Serum creatinine ≤2.5 mg/dL
  • Serum direct bilirubin <2.0 mg/dL

Key Exclusion

  • Prior therapy with interferon, pegylated interferon, or azacitidine
  • Spleen overtly enlarged by physical exam (>5 fingerbreadth below costal margin)
  • Clinically significant autoimmune disease
  • History of or current clinically relevant depression, anxiety, suicidal ideation or attempts
  • Severe retinopathy or clinically relevant ophthalmological disorder
  • Active uncontrolled infection including HIV, hepatitis B or C
  • History of malignancy within 5 years with specific exceptions
  • Pregnant or breastfeeding women

NCT07347418

Phase 1, Open Label, Dose Escalation Study to Evaluate the Safety, Expansion, Persistence, and Preliminary Clinical Activity of Autologous CD64 CAR T Cells in Patients With Relapsed and/or Refractory Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (HR-MDS) Genomic-based

Organization/Sponsor: University of Colorado, Denver


Example patient: A 52-year-old man with relapsed AML after venetoclax/azacitidine therapy, CD64-positive blasts, ECOG 1, with available stem cell backup and no active infections.

Phase 1

Interventions

  • Biological: CD64 CAR T Cells
    Summary: Autologous CAR T cells engineered to target CD64 protein expressed on myeloid leukemia cells, inducing immune-mediated destruction of AML blasts. Designed for treatment-resistant acute myeloid leukemia. Source: Web Search Summary.

Key Inclusion

  • Age ≥18 years
  • AML, MDS/AML, or MDS-EB per ICC 2022 criteria
  • Refractory or relapsed after venetoclax/HMA combination therapy
  • At least one prior line of therapy including venetoclax
  • CD64 expression on myeloid blasts by flow cytometry
  • WBC ≤25 x 10^9/L prior to apheresis
  • Confirmed availability of rescue stem cell transplant
  • ECOG performance status 0-2

Key Exclusion

  • Acute promyelocytic leukemia with t(15;17)
  • Previous gene or cell therapy including CAR therapy
  • CNS leukemia involvement
  • Active hepatitis B, hepatitis C, or HIV infection
  • Concurrent systemic steroids or immunosuppressants
  • NYHA Class III/IV cardiovascular disability
  • Prior allogeneic transplant <6 months or active GVHD
  • Pregnant or lactating women

NCT07104032

A Phase 3, Multi-regional, Open-label, Randomized Study of Tirabrutinib vs Rituximab and Temozolomide in Participants With Relapsed/Refractory Primary Central Nervous System Lymphoma

Organization/Sponsor: Ono Pharmaceutical Co., Ltd.


Example patient: A 58-year-old patient with relapsed B-cell primary CNS lymphoma after high-dose methotrexate therapy, presenting with a 1.5 cm brain lesion on MRI, ECOG PS 1, and adequate organ function.

Phase 3

Interventions

  • Drug: Temozolomide
    Summary: Temozolomide is an oral alkylating agent that converts to MTIC at physiologic pH, methylating DNA at O6 and N7 positions of guanine to inhibit DNA replication. Used for treating brain cancers including glioblastoma and anaplastic astrocytoma, it penetrates well into the CNS. Source: FDA label, NCI Thesaurus.
  • Biological: Rituximab
    Summary: Rituximab is a chimeric monoclonal antibody targeting CD20 antigen on B cells, inducing cytolysis through complement-dependent and antibody-dependent mechanisms. Indicated for CD20-positive B-cell malignancies including non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Source: FDA label, NCI Thesaurus.
  • Drug: Tirabrutinib
    Summary: Tirabrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor that covalently binds to BTK, blocking B cell receptor signaling and inhibiting B cell development, activation, and proliferation in B cell malignancies. Source: NCI Thesaurus.

Key Inclusion

  • Pathology-confirmed B-cell PCNSL
  • Relapsed or refractory disease after at least 1 prior high-dose methotrexate-based therapy
  • One or more measurable brain lesions ≥1 cm × ≥1 cm on gadolinium-enhanced MRI
  • ECOG Performance Status 0-2
  • Adequate bone marrow, renal, and hepatic function
  • Agreement to comply with contraceptive requirements

Key Exclusion

  • Isolated intraocular or spinal PCNSL without brain lesions
  • Non-B-cell PCNSL
  • Systemic presence of lymphoma
  • Refractory to temozolomide with or without rituximab in last treatment
  • Systemic corticosteroid exposure within 14 days (with specified exceptions)
  • Active malignancy other than PCNSL requiring systemic therapy
  • Prior Bruton's tyrosine kinase inhibitor treatment
  • Unable to swallow oral medication

NCT07374315

A Family-based Intervention Approach to Address Weight Gain in Pediatric Leukemia Survivors

Organization/Sponsor: Washington University School of Medicine


Example patient: A 12-year-old English-speaking patient with B-cell ALL currently on maintenance chemotherapy, able to walk briskly for five minutes, with no developmental delays or eating disorders, accompanied by a participating caregiver.

Phase N/A

Interventions

  • Educational Platform: WashU Extended Learning Canvas
    Summary: Educational platform targeting pre-leukemic conditions and employing innovative immunotherapies including CAR-T cell treatments for aggressive T cell cancers using gene editing mechanisms (Summary of Web Search).
  • Device: FitBit Ace
    Summary: Wearable activity monitor measuring steps walked, heart rate, sleep quality, steps climbed, and other fitness metrics (NCI Thesaurus).
  • Educational Resource: NIH Educational Resources
    Summary: Educational resources targeting leukemia and lymphoma patients through clinical trials focusing on innovative treatment approaches and educational interventions to improve patient outcomes (Summary of Web Search).
  • Behavioral: Modified Guided Self-Help Family Intervention
    Summary: Family-based psychological support intervention targeting families dealing with leukemia or lymphoma to improve coping strategies and emotional well-being through structured guidance and self-help techniques (Summary of Web Search).

Key Inclusion

  • Diagnosis of ALL (T or B cell)
  • Receiving standard of care maintenance chemotherapy or within 6 months of concluding maintenance
  • Age 6 to 18 years at enrollment
  • Able to speak and understand English
  • Participating caregiver required
  • Able to perform exercise for at least five minutes
  • Negative SCOFF screen for disordered eating (patients 10 and older)
  • Informed consent or assent with caregiver consent

Key Exclusion

  • Severe developmental delay or intellectual disabilities (e.g., Trisomy 21, severe autism)
  • Significant mental illness (active suicidal ideation, psychotic symptoms, manic episodes, severe substance use disorder)
  • SCOFF score of 2 or more indicating disordered eating (patients 10 and older)
  • Unable to perform any level of exercise

NCT07424833

A Phase I Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of APG-3288 in Patients With Relapsed/Refractory Hematological Malignancies

Organization/Sponsor: Ascentage Pharma Group Inc.


Example patient: A 62-year-old man with relapsed mantle cell lymphoma after three prior therapies including ibrutinib, with ECOG status 1, adequate organ function, and no cardiac disease or active infections.

Phase 1

Interventions

  • Drug: APG-3288
    Summary: APG-3288 is a novel BTK-targeted protein degrader utilizing proteolysis-targeting chimera (PROTAC) technology for treating B-cell malignancies including mantle cell lymphoma, with IND clearance from FDA and China CDE (Source: Web Search).

Key Inclusion

  • ECOG status ≤1 in dose escalation, ≤2 in dose expansion
  • Histologically or cytologically confirmed R/R CLL/SLL, DLBCL, MCL, WM, MZL, or FL
  • At least 2 prior lines of systemic therapy including BTK inhibitor for approved indications
  • Failed or not eligible for available therapies with established clinical benefit
  • Measurable disease per response criteria
  • Adequate organ and bone marrow function

Key Exclusion

  • Concurrent anti-cancer therapy
  • Prior BTK degrader treatment or allogeneic stem cell transplant
  • Persistent toxicities Grade ≥2 from prior therapy
  • Use of therapeutic-dose anticoagulants or antiplatelet agents
  • NYHA class III/IV cardiac disease or LVEF <50%
  • Symptomatic brain metastases or CNS involvement
  • Concurrent use of QT-prolonging medications
  • Autoimmune diseases or chronic inflammatory conditions

NCT07223814

Bleximenib or Placebo in Combination With Standard Induction and Consolidation Therapy Followed by Maintenance for the Treatment of Patients With Newly Diagnosed KMT2A-rearranged or NPM1-mutant Acute Myeloid Leukemia Eligible for Intensive Chemotherapy: a Double-blind Phase 3 Study Genomic-based

Organization/Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland


Example patient: A 52-year-old patient with newly diagnosed NPM1-mutant AML, 15% bone marrow blasts, ECOG status 1, normal cardiac and renal function, no prior AML treatment, eligible for intensive chemotherapy.

Phase 3

Interventions

  • Drug: Bleximenib
    Summary: An orally bioavailable protein-protein interaction inhibitor that blocks menin-MLL complex formation, reducing downstream gene expression and inhibiting proliferation of leukemic cells with KMT2A or NPM1 alterations (source: NCI Thesaurus).
  • Drug: Cytarabine
    Summary: An antimetabolite nucleoside analog that inhibits DNA synthesis by competing with cytidine during DNA replication, specifically targeting S phase of cell cycle in leukemia treatment (source: FDA label, NCI Thesaurus).
  • Drug: Daunorubicin or Idarubicin
    Summary: Anthracycline antibiotics that intercalate DNA, inhibit topoisomerase II, and generate free radicals to kill rapidly dividing cancer cells in acute myeloid leukemia chemotherapy regimens (source: Summary of Web Search).
  • Other: Placebo
    Summary: An inactive compound identical in appearance to the active treatment, used to distinguish drug action from suggestive effects in this double-blind trial (source: NCI Thesaurus).

Key Inclusion

  • ≥18 years of age at informed consent
  • New diagnosis of AML with ≥10% blasts in bone marrow or peripheral blood
  • Mutated NPM1 or recurring KMT2A rearrangements per ICC 2022 criteria
  • Eligible for intensive chemotherapy
  • WHO/ECOG performance status ≤2
  • Adequate renal and hepatic functions

Key Exclusion

  • Prior chemotherapy for AML including hypomethylating agents
  • Active leukemic CNS involvement
  • Solid organ transplant recipient
  • Recent cardiac events within 6 months or QTcF ≥470 ms or LVEF <40%
  • Prior cumulative anthracycline dose ≥500 mg/m2
  • Chronic respiratory disease requiring supplemental oxygen

NCT07177079

High-dose Ascorbate (HDA) in Combination With Azacitidine and Venetoclax (Aza/Ven) in Newly Diagnosed Acute Myeloid Leukemia (AML) Genomic-based

Organization/Sponsor: University of Iowa


Example patient: A 78-year-old patient with newly diagnosed AML without favorable cytogenetics, ECOG performance status 2, ejection fraction 45%, and no prior AML treatment or G6PD deficiency.

Phase N/A

Interventions

  • Drug: High-dose ascorbate
    Summary: High-dose ascorbate targets redox imbalance and epigenetic reprogramming in cancer cells, enhances immune activity, and has shown in vitro anticancer effects in leukemia and lymphoma (Web Search).
  • Drug: Azacitidine
    Summary: Azacitidine is a nucleoside metabolic inhibitor that reversibly inhibits DNA methyltransferase, reactivating tumor suppressor genes and disrupting RNA function, indicated for myelodysplastic syndromes and AML (FDA label, NCI Thesaurus).
  • Drug: Venetoclax
    Summary: Venetoclax is a selective BCL-2 inhibitor that binds to BCL-2 protein and restores apoptosis in tumor cells, indicated for CLL, SLL, and newly diagnosed AML in combination with hypomethylating agents (FDA label, NCI Thesaurus).
  • Drug: Decitabine
    Summary: Decitabine is a DNA methyltransferase inhibitor that incorporates into DNA causing hypomethylation and reactivation of tumor suppressor genes, indicated for myelodysplastic syndromes (FDA label, NCI Thesaurus).

Key Inclusion

  • Adults aged ≥18 unfit for intensive chemotherapy
  • Age ≥75 or ECOG performance status 2-3
  • Newly diagnosed non-APL acute myeloid leukemia
  • Severe cardiac, pulmonary, renal, or hepatic disorder
  • History of antecedent MDS without prior hypomethylating agent
  • Therapy-related AML without prior hypomethylating agent or venetoclax
  • Adequate organ function with AST/ALT ≤3.0x ULN
  • Negative pregnancy test for females of childbearing potential

Key Exclusion

  • Prior AML therapy except hydroxyurea or low-dose cytarabine
  • Hypersensitivity to ascorbate, azacitidine, decitabine, or venetoclax
  • Favorable cytogenetics: t(8;21), inv(16), bZIP CEBPA mutation
  • NPM1, IDH1, IDH2, FLT3-ITD, FLT3-TKD, or KMT2A rearrangement
  • Kidney disease needing dialysis or history of oxalate nephropathy
  • Ferritin >1000 ng/mL indicating iron overload
  • G6PD deficiency
  • On warfarin or strong CYP3A4 inducer/inhibitor without substitution