CIML NK Cells With Venetoclax for AML
NCT06152809 · Phase 1 · Boston, Massachusetts, United States
- Condition
- Leukemia
- Disease stage
- Stage I-IV
- Phase
- Phase 1
- Study type
- BIOLOGICAL, DRUG
- Intervention
- Venetoclax
- Age
- 18 Years to
- Gender
- All
- Sponsor
- Dana-Farber Cancer Institute
- Research institution
- Dana-Farber Cancer Institute
- Facility
- Brigham and Women's Hospital
- Research center
- Brigham and Women's Hospital
Summary
The purpose of this research study is to test the safety and to explore the effectiveness of infusing cytokine- induced memory-like (CIML) natural killer (NK) cells in combination with Interleukin-2 (IL-2) and standard-of-care venetoclax as a treatment for Acute Myeloid Leukemia (AML) with measurable residual disease or oligoblastic (\< 20% blasts in the bone marrow) disease. Names of the study therapies involved in this study are: * Lymphodepleting therapy with Fludarabine and Cyclophosphamide prior to CIML NK cell infusion * CIML NK (a cellular therapy) * IL-2 (a recombinant, human glycoprotein) * Venetoclax (a selective inhibitor of BCL-2 protein)
Detailed description
This is an open-label, single center phase I trial combining Cytokine-induced memory-like natural killer (CIML NK) cell therapy with low-dose IL-2 and with venetoclax as consolidation therapy in acute myeloid leukemia (AML)with measurable residual disease or oligoblastic (\< 20% blasts in the bone marrow) disease. This is the first time that CIML NK cells in combination with venetoclax will be given to humans. The U.S. Food and Drug Administration (FDA) has not approved CIML NK cells as a treatment for AML. The U.S. FDA has not approved IL-2 for AML but it has been approved for other uses. The U.S. FDA has approved venetoclax as a treatment option for AML. The research study procedures include screening for eligibility, study treatment visits, electrocardiograms (ECGs), bone marrow biopsies, blood tests, and echocardiograms. Participants will be followed for up to 1 year after the start of therapy. It is expected that about 10 people will take part in this research study. This research is funded by the Leukemia and Lymphoma Society.
Inclusion criteria
Inclusion Criteria for Trial Enrollment (Registration Visit): * Diagnosis of AML or MDS/AML (10-19% blasts) by 2022 ELN criteria. Historical test results (either peripheral blood or bone marrow) can be used to establish this diagnosis. * Age ≥ 18 years old * At time of screening patient has received any prior lines of therapy including prior chemotherapy and any prior stem cell transplant, provided that the stem cell transplant is \> 6 months ago with no ongoing need for immunosuppressive therapy for active graft-versus-host disease. * Presence of molecular risk factors for relapse as defined by any of the following present at any time during a participant's history of AML: * 2022 ELN adverse risk karyotype: t(6;9)(p23.3;q34.1)/DEK::NUP214; t(v;11q23.3)/KMT2A-rearranged; t(9;22)(q34.1;q11.2)/BCR::ABL1; t(8;16)(p11.2;p13.3)/KAT6A::CREBBP; inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/ GATA2, MECOM(EVI1), t(3q26.2;v)/MECOM(EVI1)-rearranged; -5 or del(5q); -7; Complex karyotype, monosomal karyotype * 2022 ELN adverse risk mutations: Any one of the following mutations: Mutated TP53, ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2 * Additional mutations associated with acquired resistance to venetoclax: Mutated NRAS, KRAS, FLT3 ITD/TKD * ECOG performance status ≤2 (see Appendix A) * Participants must meet the following organ function as defined below: * Direct bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN) * AST(SGOT)/ALT(SGPT): ≤3 x institutional ULN * creatinine clearance ≥ 45 mL/min; calculated by the Cockcroft Gault formula * oxygen saturation ≥ 90% on room air * left ventricular ejection fraction ≥ 40% * Negative pregnancy test for women of childbearing potential only. * The effects of CIML NK cells and IL-2 on the developing human fetus are unknown. For this reason, 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 and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and until 4 months after the last IL-2 dose administration. * Participants with current symptoms of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged) * Subjects must be able to swallow pills. * No laboratory evidence of ongoing hemolysis in the opinion of investigator (demonstration of hemolysis should include a haptoglobin level that is below assay). Exclusion Criteria for Trial Enrollment (Registration visit) * Participants are excluded if they received prior allogeneic stem cell transplant ≤ 6 months ago or require immunosuppressive therapy for active GVHD, received prior donor lymphocyte infusion (DLI) ≤ 2 months ago, or received prior organ transplant or donor lymphocyte infusion (DLI), CAR-T cell or NK cell therapy at any time. * Persisting Grade \> 2 non hematologic toxicity related to prior therapy is excluded; however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable. * Autoimmune disease: Patients with a history of inflammatory bowel disease, inc
Primary outcomes
Dose Limiting Toxicity (DLT); Maximum Tolerated Dose (MTD)
Secondary outcomes
Measurable Residual Disease Negative (MRD-) Rate; 100-day Leukemia-Free Survival (LFS); 1-year Leukemia-Free Survival (LFS)