CIML NK Cells + Venetoclax for Acute Myeloid Leukemia

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byEvan Chen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Dana-Farber Cancer Institute

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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). 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)

Research Team

Evan Chen, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with Acute Myeloid Leukemia (AML) who have had at least one cycle of HMA + venetoclax therapy, are not candidates for stem cell transplant, and have a suitable donor for NK cells. Participants must be in good health otherwise, with proper organ function and no severe allergies or autoimmune diseases.

Inclusion Criteria

Agree to use adequate contraception

No evidence of ongoing hemolysis

No severe allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study

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Exclusion Criteria

I do not have any ongoing or active infections.

I have not received any live vaccines in the past 6 months.

I am not taking strong medications that affect liver enzymes, except for antifungals.

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Treatment Details

Interventions

Cytokine-Induced Memory-like Natural Killer Cells (CAR T-cell Therapy)
Interleukin-2 (Cytokine)
Venetoclax (Anti-tumor agent)

Trial OverviewThe trial is testing the safety and potential effectiveness of CIML NK cells combined with IL-2 and venetoclax as consolidation therapy in AML patients. It includes lymphodepleting therapy before infusing the NK cells to see if this can help treat AML more effectively.

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Cohort 1: Dose Level 0Experimental Treatment3 Interventions

A maximum tolerated dose (MTD) will be established, and dosage will start at dose level 0. 5-10 participants at dose level 0 will complete: * Baseline visit. * Bone marrow biopsies: at screening visit #2, end of treatment, and at discretion of PI. * Days -6 through -2: predetermined doses of standard-of-care lymphodepleting chemotherapy. * Day 0: Predetermined dose of CIML NK cells 1x daily. Hospitalization for up to 3 to 4 weeks for CIML NK infusion. * Days 0 through 12: Predetermined dose of IL-2 1x daily every other day for up to 7 doses. * Day 7 through Day 21: Predetermined dose of Venetoclax 1 x daily. * If ≤1 dose-limiting toxicities (DLTs) are observed, this dose will be the MTD, and 5 additional participants will be enrolled. * Follow-up visits: Days 42, 60, 100 and months 6, 9, and 12.

Group II: Cohort 1: Dose Level -1Experimental Treatment3 Interventions

De-escalation to dose level -1 will be conducted per protocol if DLTs occur in Cohort 1 dose Level 0. Participants will complete: * Baseline visit. * Bone marrow biopsies: at screening visit #2, end of treatment, and at discretion of PI. * Days -6 through -2: predetermined doses of standard-of-care lymphodepleting chemotherapy. * Day 0: Predetermined dose of CIML NK cells 1x daily. Hospitalization for up to 3 to 4 weeks for CIML NK infusion. * Days 0 through 12: Predetermined dose of IL-2 1x daily every other day for up to 7 doses. * Day 7 through Day 21: Predetermined dose of Venetoclax 1 x daily. * Follow-up visits: Days 42, 60, 100 and months 6, 9, and 12.