HMA-Venetoclax Induction in Newly Diagnosed AML

Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-50
SponsorPakistan Blood and Marrow Transplant (PBMT) Group

About this trial

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.

Eligibility criteria

Qualifiers

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

Disqualifiers

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

Trial design

Treatments tested in this trial

  • 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

Treatment groups

60 Participants
are divided into 1 treatment group