CIML NK Cells With Venetoclax for AML
- Conditions
- Acute Myeloid LeukemiaAcute Myeloid Leukemia RecurrentLeukemia, MyeloidLeukemia
- Interventions
- Biological: Cytokine-Induced Memory-like Natural Killer Cells
- Registration Number
- NCT06152809
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief 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).
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).
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cohort 1: Dose Level 0 Interleukin-2 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. Cohort 1: Dose Level 0 Cytokine-Induced Memory-like Natural Killer Cells 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. Cohort 1: Dose Level -1 Cytokine-Induced Memory-like Natural Killer Cells 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. Cohort 1: Dose Level -1 Interleukin-2 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. Cohort 1: Dose Level 0 Venetoclax 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. Cohort 1: Dose Level -1 Venetoclax 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.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity (DLT) Observing window is from Day 0 (day of CIML NK cell infusion) to Day +28 A DLT is defined as an adverse event (AE) that is related to the CIML NK cell infusion with venetoclax as consolidation therapy. Toxicities are to be assessed according to the CTCAEv5.
Maximum Tolerated Dose (MTD) Observing window is from Day 0 (day of CIML NK cell infusion) to Day +28 The MTD in the CIML NK cell infusion with venetoclax as consolidation therapy is determined by the number of participants who experience a DLT. See previous primary outcome measure for the DLT definition. If ≤1 DLTs are observed at dose-level 0, this dose will be the MTD. If ≥2 DLTs are observed in a cohort of 5 evaluable participants, then the MTD is considered exceeded. If this is dose level 0, dose de-escalation will take place, and 5 evaluable participants will be enrolled at dose level -1. If ≥2 DLTs are observed at dose level -1, accrual will stop.
- Secondary Outcome Measures
Name Time Method Measurable Residual Disease Negative (MRD-) Rate At +28 days post CIML NK Infusion MRD- rate is defined as the proportion pf participants achieving MRD. MRD clearance is evaluated by both highly sensitive flow cytometry and duplex sequencing on paired bone marrow samples.
100-day Overall Survival (OS) 100 Days 100-day OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.
1-year Overall Survival (OS) 1 Year 1-year OS is a probability estimated using the Kaplan-Meier method; OS is defined as the time from study entry to death, or censored at date last known alive.
Acute GVHD Rate 1 Year Acute GVHD Rate is defined as the proportion of participants that has achieved acute GVHD. The criteria of acute GVHD grading is attached in protocol appendix c.
1-year Chronic GVHD Rate 1 Year Chronic GVHD Rate is defined as the proportion of participants that has achieved chronic GVHD by NCI common toxicity criteria (appendix d).
100-day Leukemia-Free Survival (LFS) 100 Days Leukemia free survival based on the Kaplan-Meier method is defined as the the duration of time from study entry to documented disease progression (leukemic relapse or death from any cause) or death. 100-day LFS is calculated from the KM curve with standard error.
1-year Leukemia-Free Survival (LFS) 1 Year Leukemia free survival based on the Kaplan-Meier method is defined as the the duration of time from study entry to documented disease progression (leukemic relapse or death from any cause) or death. 1-year LFS is calculated from the KM curve with standard error.
Trial Locations
- Locations (2)
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States