Reduced 14-day venetoclax cycles with azacitidine or decitabine for AML in remission

A Pilot Study of Reduced Venetoclax Exposure in Patients With Acute Myeloid Leukemia in Complete Remission

This trial tests whether giving venetoclax for 14 days each 28-day cycle alongside the same azacitidine or decitabine used in induction is better tolerated for people with AML who are in remission but not eligible for intensive therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 41 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Northwell Health (other)
• Drugs / interventions: CAR-T
• Locations: 1 site (New Hyde Park, New York)
• Trial ID: NCT07163793 on ClinicalTrials.gov

What this trial studies

This is a single-arm pilot trial that gives venetoclax for 14 days per 28-day cycle combined with the hypomethylating agent (azacitidine or decitabine) used during induction in patients who achieved morphological remission and are ineligible for intensive treatment. Participants continue the HMA and receive repeated 28-day cycles of shortened venetoclax until they experience prolonged grade 4 cytopenia, an adverse event requiring regimen modification, relapse, or death. The trial will record tolerability and cytopenia rates and compare the frequency of prolonged grade 4 cytopenia to historical results from VIALE-A. Safety monitoring and predefined stopping rules guide treatment continuation.

Who should consider this trial

Good fit: Adults with AML who achieved morphological CR/CRi (≤5% blasts) after induction with azacitidine+venetoclax or decitabine+venetoclax, are ineligible for intensive therapy, have ECOG 0–3, can take oral medication, and can enroll within the specified window after the remission biopsy.

Not a fit: Patients who are eligible for intensive chemotherapy, who have relapsed disease, or who did not receive HMA+venetoclax induction are unlikely to benefit from this specific regimen.

Why it matters

Potential benefit: If successful, this approach could reduce the rate and duration of severe cytopenias and make maintenance therapy easier to tolerate with fewer complications.

How similar studies have performed: The VIALE-A trial showed benefit for venetoclax plus azacitidine in older or unfit AML patients, but shortening venetoclax exposure to 14 days as a maintenance strategy is relatively novel with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Stated willingness to comply with all study procedures and availability for the duration of the study
2. Ability to take oral medication and be willing to adhere to the study regimen
3. Diagnosed by current WHO or ICC criteria with Acute Myeloid Leukemia and treated for initial induction therapy with one of two regimens:

   1. 5-Azacitidine administered subcutaneously at a dose of 75mg/m2/day X 7 days in combination with VEN (21-28 days/cycle)
   2. Decitabine administered intravenously at a dose of 20mg/m2/day administered in combination with VEN (21-28 days/cycle)
4. Achieving morphological CR/CRi by bone marrow biopsy with \<5% blasts within 3 cycles. See Appendix 2 for definitions.
5. Consent to be obtained within 10 days (+/- 3 days) of bone marrow biopsy report showing morphological remission. C1D1 of trial to be initiated within 10 days (+/- 7 days) of bone marrow biopsy report showing morphological remission.
6. ECOG 0-3
7. Intensive treatment ineligible; transplant ineligible or refusal of transplant
8. Patient must be able to understand and sign informed consent and additional study documents
9. On C1D1 of trial, patient must have count recovery with ANC \>1000, platelets \> 50, Hemoglobin \> 7.7 and without transfusion support for 7 days.
10. No growth factor (G-CSF) use in 14 days prior to C1 D1 of trial.

Exclusion Criteria:

1. Treatment with another investigational drug
2. Use of growth factor (G-CSF) within the last 14 days prior to C1D1 of trial treatment.
3. On concomitant targeted therapy such as FLT3 inhibitor or IDH1/2 inhibitor.
4. Subject has received treatment prior to induction with the following:

   i. Prior hypomethylating agent or BCL-2 inhibitor for either AML or MDS other than for induction prior to enrollment.

   ii. Prior CAR-T cell therapy. iii. Experimental or investigational drug therapy for 14 days prior to study entry leukemia-directed therapies.
5. Subject has:

   i. Acute promyelocytic leukemia (APL) with t(15;17). ii. Presence of t(9;22) given the potential indication for concurrent tyrosine kinase therapy.

   iii. Known active CNS involvement with AML.

Where this trial is running

New Hyde Park, New York

• Zuckerberg Cancer Center — New Hyde Park, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Boiclair Stephanie, MD — Northwell Health
• Study coordinator: Heme Referral Team

Conditions: Acute Myeloid Leukemia in Remission, AML