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)

NCT06158100 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: 20230190
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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

Keywords

Hematopoietic Cell Transplant (HCT)

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  The RP2D of VEN/AZA therapy will be determined as the maximum tolerated dose of study treatment as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Up to 13 months

• Number of Participants Experiencing Treatment-Related Toxicity

  The number of participants experiencing treatment-related toxicity. Toxicity is defined as including dose limiting toxicities (DLTs), serious adverse events (SAEs) and adverse events (AEs) in study participants after starting study therapy. Toxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.

  Up to 13 months

Secondary Outcomes (5)

• Recurrence-Free Survival (RFS)

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

• Proportion of Participants with Treatment-Related Mortality (TRM)

  180 days

• Number of Participants with acute GVHD After Allogeneic Hematopoietic Cell Transplant (HCT)

  Up to 180 days

• Number of Participants with chronic GVHD After Allogeneic Hematopoietic Cell Transplant (HCT)

  1 year

Study Arms (2)

VEN/AZA Dose Escalation/De-Escalation Cohort

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Azacitidine; Biological: Donor Lymphocyte Infusion

VEN/AZA Expansion Cohort

EXPERIMENTAL

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.

Drug: Venetoclax; Drug: Azacitidine; Biological: Donor Lymphocyte Infusion

Interventions

Venetoclax 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.

Also known as: Venclexta, Venclyxto

VEN/AZA Dose Escalation/De-Escalation Cohort; VEN/AZA Expansion Cohort

Azacitidine 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.

Also known as: Vidaza, Azadine

VEN/AZA Dose Escalation/De-Escalation Cohort; VEN/AZA Expansion Cohort

Donor Lymphocyte Infusion 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 Dose Escalation/De-Escalation Cohort; VEN/AZA Expansion Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients between the ages of 18-75.
• 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.
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Serum creatinine =\< 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min
• Serum bilirubin =\< 1.5 x upper limit of normal (ULN)
• Aspartate transaminase (AST) or alanine transaminase (ALT) =\< 2.5 x ULN
• Alkaline phosphatase =\< 2.5 x UL
• Negative serum or urine pregnancy test for women with reproductive potential.
• A negative donor-specific antibody (DSA) assay (i.e., Micro-Flow Imaging (MFI) \<m3000) for recipients of any mismatched graft (including haploidentical) HCT.

You may not qualify if:

• Active disease (\>5% blasts or any evidence of extra-medullary disease) at the time of transplantation or at day +30
• Active acute graft-versus-host disease (aGVHD) requiring systemic IST or history of aGVHD grade III or higher.
• Active chronic GVHD requiring systemic immunosuppressive therapy (IST).
• Active uncontrolled systemic fungal, bacterial, or viral infection
• Known active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
• 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.
• 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.

Sponsors & Collaborators

• Antonio M Jimenez Jimenez: lead
• AbbVie: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine

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

• Antonio M Jimenez Jimenez, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical

Model Details: Phase 1 dose escalation/de-escalation and dose expansion design.

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 6, 2023
• Study Start: December 4, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)