Venetoclax in Combination With Azacitidine (VEN/AZA) Followed by Donor Lymphocyte Infusion (DLI) for Patients With Very High-Risk Acute Myeloid Leukemia (AML) Undergoing Allogeneic Hematopoietic Cell Transplant (HCT)

NCT ID: NCT06158100

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-04
• Study Completion Date: 2027-12-31

Brief Summary

The purpose of this study is to see the effects of an investigational combination treatment of venetoclax, azacitidine, and donor lymphocyte infusion (DLI) in patients with high-risk AML receiving allogeneic hematopoietic cell transplantation, and to assess if the combination treatment is well tolerated and prevents disease relapse after transplant.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VEN/AZA Dose Escalation/De-Escalation Cohort

Participants in this group will begin Venetoclax and Azacitidine (VEN/AZA) combination therapy between day +42 and day +100 following hematopoietic cell transplant (HCT) infusion. VEN/AZA combination therapy will be administered for up to six (6) cycles, followed by up to six (6) additional cycles of Venetoclax monotherapy in the absence of disease progression or unacceptable toxicity. Each cycle is 28 days.

Participants may also receive donor lymphocyte infusions (DLI) at the discretion of the treating physician, if certain criteria are met.

Participants will receive up to one year (12 cycles) of study therapy, followed by up to one year of follow-up. Total participation duration is up to two years.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax will be given orally (PO) at the assigned doses of 50 or 100 mg once daily for 7, 14 or 21 days starting at day 1 of each 28-day cycle, for up to 12 cycles.

Azacitidine

Intervention Type: DRUG

Azacitidine will be administered at a dose of 20mg/m\^2 once daily subcutaneously (SC) or intravenously (IV) for five days (Days 1-5) of each 28-day cycle.

Donor Lymphocyte Infusion

Intervention Type: BIOLOGICAL

Donor lymphocyte infusions (DLI) may be administered at the discretion of the treating physician, if certain criteria are met. Participants may receive up to three (3) infusions of donor lymphocytes (a type of white blood cell) at the following dose levels and study timepoints:

• DLI 1: 1x10^6 cluster of differentiation 3+ (CD3+) cells/kg, after cycle 3
• DLI 2: 5x10^6 CD3+ cells/kg, after cycle 5, if there is persistent MRD
• DLI 3: 1x10^7 CD3+ cells/kg, after cycle 7, if there is persistent MRD.

VEN/AZA Expansion Cohort

Participants in this group will receive VEN/AZA therapy at the most appropriate dose determined in Part 1. Participants may also receive donor lymphocyte infusions (DLI) at the discretion of the treating physician, if certain criteria are met.

Participants will receive up to one year (12 cycles) of study therapy, followed by up to one year of follow-up. Total participation duration is up to two years.

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax will be given orally (PO) at the assigned doses of 50 or 100 mg once daily for 7, 14 or 21 days starting at day 1 of each 28-day cycle, for up to 12 cycles.

Azacitidine

Intervention Type: DRUG

Azacitidine will be administered at a dose of 20mg/m\^2 once daily subcutaneously (SC) or intravenously (IV) for five days (Days 1-5) of each 28-day cycle.

Donor Lymphocyte Infusion

Intervention Type: BIOLOGICAL

Donor lymphocyte infusions (DLI) may be administered at the discretion of the treating physician, if certain criteria are met. Participants may receive up to three (3) infusions of donor lymphocytes (a type of white blood cell) at the following dose levels and study timepoints:

• DLI 1: 1x10^6 cluster of differentiation 3+ (CD3+) cells/kg, after cycle 3
• DLI 2: 5x10^6 CD3+ cells/kg, after cycle 5, if there is persistent MRD
• DLI 3: 1x10^7 CD3+ cells/kg, after cycle 7, if there is persistent MRD.

Interventions

Venetoclax

Venetoclax will be given orally (PO) at the assigned doses of 50 or 100 mg once daily for 7, 14 or 21 days starting at day 1 of each 28-day cycle, for up to 12 cycles.

Intervention Type: DRUG

Azacitidine

Azacitidine will be administered at a dose of 20mg/m\^2 once daily subcutaneously (SC) or intravenously (IV) for five days (Days 1-5) of each 28-day cycle.

Intervention Type: DRUG

Donor Lymphocyte Infusion

Donor lymphocyte infusions (DLI) may be administered at the discretion of the treating physician, if certain criteria are met. Participants may receive up to three (3) infusions of donor lymphocytes (a type of white blood cell) at the following dose levels and study timepoints:

• DLI 1: 1x10^6 cluster of differentiation 3+ (CD3+) cells/kg, after cycle 3
• DLI 2: 5x10^6 CD3+ cells/kg, after cycle 5, if there is persistent MRD
• DLI 3: 1x10^7 CD3+ cells/kg, after cycle 7, if there is persistent MRD.

Intervention Type: BIOLOGICAL

Other Intervention Names

Venclexta; Venclyxto; Vidaza; Azadine

Eligibility Criteria

Inclusion Criteria

1. Male and female patients between the ages of 18-75.

2. Patients with a histologic diagnosis of AML in morphological remission (<5% bone marrow (BM) blasts) prior to allogeneic hematopoietic cell transplantation and very high-risk for relapse defined as: (i) Presence of measurable residual disease (MRD) by multicolor flow cytometry (MFC) prior to transplant and receiving a reduced intensity conditioning (RIC) or nonmyeloablative (NMA) regimen (ii) Presence of MRD by MFC at day +30 post-transplant (iii) All patients with monosomal karyotype (MK) and those with 17p/tumor protein p53 (TP53) mutated disease irrespective of MRD status and intensity of conditioning regimen.

3. Adequate hematopoietic recovery after HCT, defined as:

• Absolute neutrophil count (ANC) >= 1 x 10^9/L without daily use of myeloid growth factors
• Platelet count >= 50 x 10^9/L without platelet transfusion within 1 week

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

5. Serum creatinine =< 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min

6. Serum bilirubin =< 1.5 x upper limit of normal (ULN)

7. Aspartate transaminase (AST) or alanine transaminase (ALT) =< 2.5 x ULN

8. Alkaline phosphatase =< 2.5 x UL

9. Negative serum or urine pregnancy test for women with reproductive potential.

10. A negative donor-specific antibody (DSA) assay (i.e., Micro-Flow Imaging (MFI) <m3000) for recipients of any mismatched graft (including haploidentical) HCT.

Exclusion Criteria

1. Active disease (>5% blasts or any evidence of extra-medullary disease) at the time of transplantation or at day +30

2. Active acute graft-versus-host disease (aGVHD) requiring systemic IST or history of aGVHD grade III or higher.

3. Active chronic GVHD requiring systemic immunosuppressive therapy (IST).

4. Active uncontrolled systemic fungal, bacterial, or viral infection

5. Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)

6. Significant active cardiac disease within the previous 6 months, including: New York Heart Association (NYHA) class III or IV congestive heart failure. Unstable angina, angina requiring surgical or medical intervention, and/or myocardial infarction.

7. History of any other malignancy within 2 years prior to study entry, except for: adequately treated in situ carcinoma of the cervix or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; myelodysplastic syndrome.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: collaborator

Antonio M Jimenez Jimenez

OTHER

Sponsor Role: lead

Responsible Party

Antonio M Jimenez Jimenez

Associate Professor of Clinical

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Antonio M Jimenez Jimenez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

20230190

Identifier Type: -

Identifier Source: org_study_id