Venetoclax-based therapy combined with donor microtransplant for newly diagnosed AML

Phase 2 Study of Venetoclax-containing Therapy in Combination With HLA-mismatched Mobilized Peripheral Blood Mononuclear Cell Infusion for Newly Diagnosed Acute Myeloid Leukemia

This will test whether giving HLA-mismatched donor G-CSF mobilized blood cells alongside venetoclax-containing therapy helps adults newly diagnosed with AML live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing 302 Hospital (other)
• Locations: 1 site (Beijing)
• Trial ID: NCT07078591 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial combines venetoclax-containing regimens with HLA-mismatched donor G-CSF mobilized peripheral blood mononuclear cell (GPBMC) infusions, a technique referred to as microtransplant. Adult patients with newly diagnosed acute myeloid leukemia who meet organ-function and WBC criteria are treated with standard chemotherapy/azacitidine plus venetoclax and receive GPBMC infusions from a partly mismatched donor. Donors must be aged 18 or older and have at least three HLA loci mismatched (0–7/10 match). The study will track safety, remission rates, and survival outcomes to see if the microtransplant addition improves patient outcomes compared with historical expectations.

Who should consider this trial

Good fit: Adults aged 18 or older with newly diagnosed AML, WBC <25×10^9/L, adequate liver, kidney and cardiac function, no prior anti-leukemia therapy (except hydroxyurea), and an eligible HLA-mismatched donor willing to donate.

Not a fit: Patients without an eligible or willing mismatched donor, those with poor organ function or prior AML-directed therapy, or those with very high WBC counts may not be eligible and are less likely to benefit from this approach.

Why it matters

Potential benefit: If successful, the combination could increase remission rates and overall survival for some adults with newly diagnosed AML.

How similar studies have performed: Venetoclax-based combinations have shown meaningful benefit in AML in prior studies, but the addition of HLA-mismatched GPBMC microtransplantation is a more experimental strategy with limited published evidence.

Eligibility criteria

Inclusion Criteria:

* 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.
* Donor inclusion criteria: The donor meets the institution's criteria for related peripheral blood hematopoietic stem cell donors. The donor must be able to tolerate the cell separation and collection process, and sign the Informed Consent Form.

Exclusion Criteria:

* 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.

Where this trial is running

Beijing

• Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital — Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Bo Cai, MD — Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital
• Study coordinator: Bo Cai, MD

Conditions: Acute Myeloid Leukemia, venetoclax, microtransplant, microtransplantation