Combining CLAG-M therapy with venetoclax for relapsed or refractory acute myeloid leukemia

A Prospective, Multicenter, Randomized, Open-Label, Phase II Study of Salvage BCL2i Plus CLAG-M in Relapsed or Refractory Acute Myeloid Leukemia

This study is testing if adding a drug called venetoclax to a standard treatment for relapsed or refractory acute myeloid leukemia can help patients feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 52 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 2 sites (Tampa, Florida and 1 other locations)
• Trial ID: NCT06660368 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label phase II study investigates the combination of CLAG-based therapy with or without venetoclax in patients suffering from relapsed or refractory acute myeloid leukemia (AML). The goal is to enhance measurable residual disease (MRD) clearance and improve event-free survival rates. Researchers hypothesize that adding venetoclax to the CLAG-M regimen will be safe and more effective than CLAG-M alone in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with documented relapsed or refractory AML.

Not a fit: Patients with AML that is not relapsed or refractory may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to better treatment outcomes and longer survival for patients with relapsed or refractory AML.

How similar studies have performed: Other studies have shown promise in using venetoclax in combination therapies for AML, suggesting potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* Provision of signed and dated informed consent form.
* Ability to understand and stated willingness to comply with all study procedures and availability for the duration of the study.
* Adults aged ≥18 years - 80 years.
* Patients with documented refractory or relapsed AML: Refractory disease is defined as failure to achieve CR (i.e., \<5% blasts in BM or blood) with or without normal restoration of hematopoiesis (Cri) after at least 1 cycle of intensive induction therapy (or 2 cycles of non-intensive induction). Relapse: Recurrence of disease after achieving remission, meeting one or more of the following criteria: ≥ 5% blasts in the marrow or peripheral blood, extramedullary disease.
* Secondary AML arising out of MDS previously treated with HMA, HMA + venetoclax (if \> 3 months from venetoclax exposure), and/or 1 cycle of induction chemotherapy.
* Extramedullary AML with marrow involvement is allowed as long as concurrent medullary AML is present.
* ECOG performance status ≤ 2.
* Participants must have adequate organ function as defined within the protocol.
* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not mandatory.
* For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and have an undetectable HCV viral load. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. Testing is not mandatory.
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 4 months after completion of study drug administration.

Exclusion Criteria:

* Venetoclax-refractory disease or recent venetoclax exposure \< 3 months prior to first dose of study therapy.
* Prior treatment with a high-dose cytarabine-containing regimen (e.g., no prior CLAG/FLAG/MEC/CLIA/HAM, etc.).
* Allogeneic stem cell transplant in the past 3 months.
* Less than 14 days from last AML-directed therapy or five half-lives, whichever is shorter, not including hydroxyurea.
* Known history of prior TP53 mutation (results from any myeloid mutation panel are not required for screening eligibility).
* Active CNS involvement by AML.
* WBC count ≥25k at the time study treatment begins.
* Uncontrolled intercurrent systemic illness that would limit compliance.
* Concurrent malignancy in addition to AML that requires active treatment with some exceptions.
* Immunosuppressive therapy in the past 14 days except for prednisone at ≤ 10 mg/day or equivalent AND no active or uncontrolled graft-versus-host disease (GvHD).
* Participants who have not recovered from adverse events (Aes) due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1), with the exception of alopecia.
* Participants who are receiving any other investigational agents.
* Participants with psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active heart disease that limits the use of mitoxantrone or recent (\<6 months) history of an acute cardiovascular event (STEMI, NSTEMI).
* Pregnant women are excluded from this study because venetoclax, cladribine, and cytarabine are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these drugs, breastfeeding should be discontinued.

Where this trial is running

Tampa, Florida and 1 other locations

• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (Not_yet_recruiting)

Study contacts

• Principal investigator: David Sallman, MD — Moffitt Cancer Center
• Study coordinator: Quan Lovette

Conditions Relapsed or Refractory Acute Myeloid Leukemia