HMA-Venetoclax Induction in Newly Diagnosed AML

NCT07748455 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: AFBMTC-AML-VEN-2026
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Acute myeloid leukaemia (AML) is a clonal haematological malignancy characterised by arrested myeloid differentiation and uncontrolled proliferation of blast cells in the bone marrow and peripheral blood. It is the most common acute leukaemia in adults and carries a high disease-related mortality. Globally, the median age of diagnosis is approximately 68 years; however, a significant proportion of patients are diagnosed below the age of 50 years, constituting the 'young fit' population for whom aggressive curative-intent therapy is most appropriate. The epidemiology of AML in South Asia and Pakistan remains incompletely characterised. Published single-centre and multi-centre data from Pakistan suggest that AML represents a major proportion of haematological malignancies presenting to tertiary centres. AFBMTC, as the largest haematology and transplant centre in Pakistan, has accumulated over 2,000 HSCT procedures since 2001 and has established the necessary infrastructure for prospective clinical research in this disease. Cytogenetic and molecular classification of AML profoundly influences prognosis and treatment decisions. The European LeukemiaNet (ELN) 2022 risk stratification framework categorises AML into Favourable, Intermediate, and Adverse risk groups based on chromosomal abnormalities and somatic mutations including NPM1, FLT3-ITD, IDH1/2, RUNX1, ASXL1, TP53, and others. This framework underpins post-remission pathway assignment in the current protocol.

Conditions

AML; AML (Acute Myeloid Leukemia)

Keywords

AML, Azacytidine, Venetoclax, LMIC

Outcome Measures

Primary Outcomes (1)

• Remission rate after Aza-Ven Therapy

  Composite complete remission rate: proportion of patients achieving CR, CRi, or CRh as assessed by treating haematologist per ELN 2022 response criteria on bone marrow assessment at Day 28-35 of Cycle 1 (and after Cycle 2 for non-responders).

  At the end of each cycle from Day 28-35 of Cycle (duration of each cycle is 28 days)

Secondary Outcomes (1)

• EFS, OS, MRD, HSCT conversion rate

  12-24 months

Other Outcomes (1)

• Mutation association

  12-24 months

Study Arms (1)

Aza-Ven Arm

OTHER

Induction Regimen: AZA-VEN The AZA-VEN induction regimen will be administered for a maximum of 2 cycles (each 28 days). Patients achieving CR/CRi/CRh after Cycle 1 will proceed directly to post-remission therapy. Drug Dose Route Days Cycle Duration Azacitidine 75 mg/m² SC or IV infusion (30 min) Days 1-7 28 days (repeat Cycle 2 if needed) Venetoclax 400 mg/day (target; after ramp-up) Oral (once daily with food or within 30 min of eating) Days 1-28 28 days Venetoclax Ramp-Up Schedule (Cycle 1 Only) To mitigate the risk of tumour lysis syndrome (TLS), venetoclax must be dose-ramped during Cycle 1. The ramp-up is not required in subsequent cycles. Days Daily Dose TLS Risk Mitigation Day 1 100 mg Hospitalise; IV hydration; allopurinol 300 mg/day initiated ≥48h before Day 2 200 mg Continue hydration; monitor electrolytes at 4, 8, 24h post first dose Day 3 400 mg (target) Continue hydration; check electrolytes at 4h post dose Day 3 Days 4-28 400 mg Outpatient permissible if TLS risk r

Drug: Azacitidine 75 mg/m² SC/IV Days 1-7 + Venetoclax 400 mg orally Days 1-28 (Cycle 1 ramp-up per institutional TLS protocol); 28-day cycles; maximum 2 induction cycles

Interventions

Azacitidine 75 mg/m² SC/IV Days 1-7 + Venetoclax 400 mg orally Days 1-28 (Cycle 1 ramp-up per institutional TLS protocol); 28-day cycles; maximum 2 induction cycles DRUG

Induction Regimen: AZA-VEN The AZA-VEN induction regimen will be administered for a maximum of 2 cycles (each 28 days). Patients achieving CR/CRi/CRh after Cycle 1 will proceed directly to post-remission therapy. Drug Dose Route Days Cycle Duration Azacitidine 75 mg/m² SC or IV infusion (30 min) Days 1-7 28 days (repeat Cycle 2 if needed) Venetoclax 400 mg/day (target; after ramp-up) Oral (once daily with food or within 30 min of eating) Days 1-28 28 days Venetoclax Ramp-Up Schedule (Cycle 1 Only) To mitigate the risk of tumour lysis syndrome (TLS), venetoclax must be dose-ramped during Cycle 1. The ramp-up is not required in subsequent cycles. Days Daily Dose TLS Risk Mitigation Day 1 100 mg Hospitalise; IV hydration; allopurinol 300 mg/day initiated ≥48h before Day 2 200 mg Continue hydration; monitor electrolytes at 4, 8, 24h post first dose Day 3 400 mg (target) Continue hydration; check electrolytes at 4h post dose Day 3 Days 4-28 400 mg Outpatient permissible if TLS risk re

Aza-Ven Arm

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients must satisfy ALL of the following criteria to be eligible for enrolment:
• Age 18-50 years (inclusive) at the time of enrolment
• Confirmed diagnosis of AML (non-APL) per WHO 2022 Classification: ≥20% blasts in bone marrow or peripheral blood, or documented leukaemia-defining cytogenetic abnormality regardless of blast count (e.g. t(8;21), inv(16), t(15;17) is excluded as APL). Diagnosis must be confirmed by bone marrow aspirate and/or biopsy with morphology, flow cytometry, and cytogenetics.
• Newly diagnosed AML: no prior cytotoxic therapy for AML (excluding hydroxyurea for blast cytoreduction, which is permitted for ≤7 days prior to enrolment)
• ECOG Performance Status 0-2
• Adequate end-organ function at screening (within 7 days of first study drug administration):
• Serum creatinine ≤2 × ULN or CrCl ≥40 mL/min (CKD-EPI formula)
• ALT and AST ≤3 × ULN (≤5 × ULN if attributed to hepatic leukaemic infiltration)
• Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert syndrome or hepatic leukaemic infiltration)
• LVEF ≥45% by echocardiography or MUGA (assessed within 28 days of enrolment)
• Willing and able to provide written informed consent (patient or legally authorised representative for patients with AMS at presentation)
• Willingness to comply with all study procedures, including bone marrow assessments, follow-up visits, and MRD monitoring
• For women of childbearing potential (WOCBP): negative serum or urine pregnancy test within 72 hours of Cycle 1 Day 1, and agreement to use effective contraception throughout study treatment and for 12 months after last dose

You may not qualify if:

• Patients will be excluded from participation if ANY of the following apply:
• Acute promyelocytic leukaemia (APL) \[t(15;17); PML-RARA\]: patients with APL must be referred for ATRA-based therapy as per institutional standard
• AML secondary to myeloproliferative neoplasm (MPN) in blast phase, where prior MPN was treated with ruxolitinib within 8 weeks of enrolment (due to drug interaction potential with venetoclax)
• Prior exposure to a BCL-2 inhibitor (venetoclax, navitoclax, or other) at any time
• Prior exposure to HMA therapy (azacitidine or decitabine) for a pre-existing MDS or MPN within 6 months of AML diagnosis
• Known active hepatitis B virus (HBV) infection (HBsAg positive) without established antiviral prophylaxis; or active hepatitis C virus (HCV) infection with detectable viral load
• Known HIV infection with CD4 count \<350 cells/μL or detectable viral load (HIV-positive patients with well-controlled disease on antiretroviral therapy may be enrolled after discussion with the Principal Investigator and Infectious Disease consultant)
• QTcF \>480 ms on screening ECG
• Clinically significant and uncontrolled arrhythmia
• NYHA Class III-IV heart failure
• Acute coronary syndrome or stroke within 6 months of enrolment
• Malabsorption syndrome or other gastrointestinal condition that would significantly impair oral absorption of venetoclax
• Concomitant strong CYP3A4 inhibitors (e.g. ketoconazole, posaconazole, voriconazole, clarithromycin) or inducers (e.g. rifampicin, phenytoin, carbamazepine) that cannot be safely discontinued or dose-adjusted. (Note: azole antifungals require venetoclax dose reduction per label - see Section 7.4)
• Concurrent active malignancy requiring systemic therapy (patients with adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix are eligible)
• Pregnancy or breastfeeding

Sponsors & Collaborators

• Pakistan Blood and Marrow Transplant (PBMT) Group: lead

Study Sites (1)

National University of Medical Sciences, Clinical Trial Unit

Rawalpindi, 46000, Pakistan

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Raheel Iftikhar, MBBS,FCPS(Med),FCPS(Cl Haem)

  National University of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Maryam Khan, MBBS, MRCP(UK),FCPS (Cl Haem)

CONTACT

+923366395758; maryam.khan9882@gmail.com

Kashaf ad Duja Awais, MBBS, MD

CONTACT

+923326722200; kashafaddujaawais@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase II (Single-Arm Prospective)

Study Record Dates

• First Submitted: July 28, 2026
• First Posted: August 5, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 5, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 1st Jan 2028 till 31st dec 2028
• Access Criteria: Anyone can assess IPD upon request

Locations

PA (1)