Venetoclax-containing Therapy Combined With Microtransplant for Newly Diagnosed AML

NCT07078591 | Recruiting Phase 2

• 1 other identifier: VEN-MST for AML
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate whether HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusion with venetoclax-containing regimens (microtransplant, MST) could improve survival in adult patients with newly diagnosed acute myeloid leukemia (AML).

Conditions

Acute Myeloid Leukemia

Keywords

venetoclax; microtransplant; microtransplantation

Outcome Measures

Primary Outcomes (2)

• Overall survival (OS)

  OS is defined as the number of days from the date of initiation of treatment to the date of death.

  Measured up to 4 years after the last participant is enrolled

• Event-free Survival (EFS)

  EFS is defined as the number of days from initiation of treatment to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.

  Measured up to 4 years after the last participant is enrolled

Secondary Outcomes (3)

• Complete remission (CR) and complete remission with incomplete marrow recovery (CRi)

  Measured up to 2 years after the last participant is enrolled

• Partial remission (PR)

  Measured up to 2 years after the last participant is enrolled

• Non-relapse Mortality (NRM)

  Measured up to 4 years after the last participant is enrolled

Study Arms (2)

Participants fit for intensive therapy

EXPERIMENTAL

This cohort will include patients fit for intensive therapy. Induction phase: Genetically low-risk patients Venetoclax 100mg on Day 4, 200mg on Day 5, 400mg on Days 6-11 orally; Daunorubicin 60mg/m2 or idarubicin 12mg/m2 IV daily on Days 1-3; Cytarabine 100mg/m2 IV daily on Days 1-7. No more than two cycles. Continue to consolidation phase if achieving CR/CRi. Genetically intermediate/high-risk patients Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Patients \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Patients ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles.

Drug: Venetoclax; Drug: Azacitidine (AZA); Drug: Daunorubicin; Drug: Idarubicin（IDA）; Drug: Cytarabine (Ara-C); Biological: GPBMC infusion

Participants unfit for intensive therapy but fit for lower intensity therapy

EXPERIMENTAL

This cohort will include patients unfit for intensive therapy but fit for lower intensity therapy at diagnosis according to Ferrara 2013 criteria. Induction phase: Venetoclax 100mg on Day 1, 200mg on Day 2, 400 mg on Days 3-28 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. 28 days per cycle, and no more than two cycles. Re-evaluate unfitness and continue to consolidation phase if achieving CR/CRi and refuse allogeneic HSCT. Consolidation phase: Convert to "fit" patients and \< 60 years Cytarabine 1.5g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Convert to "fit" patients and ≥ 60 years Cytarabine 1g/m2 IV every 12 hours on Days 1, 2, 3; Venetoclax 400mg on Days 1-7. Infuse donor GPBMCs on Day 8. Totally 3-4 cycles. Still "unfit" patients Venetoclax 400 mg on Days 1-14 orally; Azacitidine 75mg/m2 SC daily on Days 1-7. Infuse donor GPBMCs on Day 15. 28 days per cycle until progression or untolerated.

Drug: Venetoclax; Drug: Azacitidine (AZA); Drug: Cytarabine (Ara-C); Biological: GPBMC infusion

Interventions

Venetoclax DRUG

Given PO

Participants fit for intensive therapy; Participants unfit for intensive therapy but fit for lower intensity therapy

Azacitidine (AZA) DRUG

Given SC

Participants fit for intensive therapy; Participants unfit for intensive therapy but fit for lower intensity therapy

Daunorubicin DRUG

Given IV

Participants fit for intensive therapy

Idarubicin（IDA） DRUG

Given IV

Participants fit for intensive therapy

Cytarabine (Ara-C) DRUG

Given IV

Participants fit for intensive therapy; Participants unfit for intensive therapy but fit for lower intensity therapy

GPBMC infusion BIOLOGICAL

HLA-mismatched donor GPBMC infusion

Participants fit for intensive therapy; Participants unfit for intensive therapy but fit for lower intensity therapy

Eligibility Criteria

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

You may qualify if:

• Age \>=18 years, male or female, non-limited by race or ethnicity.
• No prior anti-acute leukemia treatment (including hypomethylators for leukemia or MDS) with the exception that prior hydroxyurea and/or leukapheresis are permitted.
• Confirmed acute myeloid leukemia in accordance with WHO criteria with a WBC count \< 25 × 109/L.
• Adequate hepatic function including alanine transaminase (ALT) and aspartate aminotransferase (AST )\<= 3 × upper limit of normal(ULN), and total bilirubin \<= 1.5 × ULN.
• Adequate renal function including serum creatinine \<= 2 × ULN or CrCl\>= 40mL/min.
• LVEF measured by echocardiogram is within the normal range (LVEF \> 50%).
• The subject must have one donor who is \>= 18 years old and HLA matched at 0-7/10 loci (i.e., at least 3 HLA loci must be mismatched). In addition, the donor voluntarily donates hematopoietic stem cells and signs the consent form.
• Each subject (or his/her legal representatives) must sign the Informed Consent Form (ICF), indicating that he/she understands the purpose and procedures of research, and is willing to participate in research.

You may not qualify if:

• Acute promyelocytic leukemia, myeloid sarcoma, chronic myeloid leukemia accelerated phase and blast crisis.
• Uncontrolled infection or hemorrhage.
• Cardiovascular disease with clinical significance, such as uncontrolled or highly symptomatic cardiac arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or New York Heart Association (NYHA) function class 3 (moderate) or class 4 (severe) heart disease.
• Uncontrolled autoimmune disease or requiring immunosuppression treatment.
• History of severe blood infusion reaction.
• Nursing women, women of childbearing potential with positive urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception.
• Psychiatric disorder or cognitive impairment that in the researcher's judgment would make the subject not likely to adhere to the protocol requirements.
• Any major surgery within 4 weeks before enrollment.
• Life-threatening illness other than AML or uncontrolled intercurrent illness.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

Beijing, 100071, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax; Azacitidine; Daunorubicin; Cytarabine

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; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Arabinonucleosides

Study Officials

• Bo Cai, MD

  Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bo Cai, MD

CONTACT

+861066947168; caibo2008@163.com

Yangyang Lei, MD

CONTACT

+861066947180; 942056176@qq.com

Study Design

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

Study Record Dates

• First Submitted: July 14, 2025
• First Posted: July 22, 2025
• Study Start: June 20, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)