Preemptive CIML NK Cell Therapy After Hematopoietic Stem Cell Transplantation
- Conditions
- Myeloproliferative NeoplasmLeukemiaMyeloproliferative DisordersMyelodysplastic SyndromesAcute Myeloid LeukemiaLeukemia, Myeloid
- Interventions
- Biological: Cytokine Induced Memory-like Natural Killer Cells
- Registration Number
- NCT06138587
- Lead Sponsor
- Dana-Farber Cancer Institute
- Brief Summary
The purpose of this research study is to test the safety and efficacy of cytokine induced memory-like (CIML) natural killer (NK) cells expanded with Interleukin-2 (IL-2) at preventing relapse in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or MDS and myeloproliferative neoplasm (MPN) overlap syndrome after a standard-of-care stem cell transplant.
Names of the study therapies involved in this study are:
* CIML NK cells intravenous infusion (cellular therapy)
* Subcutaneous Interleukin-2 (recombinant, human glycoprotein)
- Detailed Description
This is a phase I/Ib study of the pre-emptive treatment using related donor-derived cytokine induced memory-like (CIML) natural killer (NK) cells combined with Interleukin-2 (IL-2) for participants with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and MDS/myeloproliferative neoplasm (MDS/MPN) overlap syndrome at high risk for post-allogeneic stem cell transplant (SCT) relapse.
The U.S. Food and Drug Administration (FDA) has not approved CIML NK cells as a treatment for AML, MDS or MDS and MPN overlap syndrome.
The research study procedures include screening for eligibility, intravenous infusion of CIML NK cells in the hospital, standard-of-care stem cell infusion, subcutaneous interleukin-2 (IL-2) infusions, x-rays, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission Tomography (PET) scans, blood tests, bone marrow biopsies, echocardiograms, and electrocardiograms.
Participation in this research study is expected to last up to 3 years.
It is expected that up to 15 people will take part in this research study.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 1/1b: CIML NK Cells + Interleukin-2 Cytokine Induced Memory-like Natural Killer Cells 5 eligible participants will be enrolled to determine the maximum tolerated dose (MTD) of CIML NK at starting dose level 0. * Screening and baseline visit with assessments and bone marrow aspirate and biopsy. * Day 0: Standard-of-care conditioning chemotherapy and stem cell infusion. * Day 7: Predetermined dose of CIML NK cells 1x daily. * Days 7, 9, 11, 13, 15: Predetermined dose of Interleukin-2 1x daily every other day (5 doses total). * Dose limiting toxicity period for 6 weeks after infusion of CIML NK cells If 0 or 1 dose limiting toxicity is observed at the dose level, then this dose will be the MTD and study will proceed to Phase 1b. De-escalation to dose level -1 per protocol if ≥2 DLTs occur with dose Level 0. In phase Ib, 10 additional participants will be enrolled at the maximum tolerated dose. Phase 1/1b: CIML NK Cells + Interleukin-2 Interleukin-2 5 eligible participants will be enrolled to determine the maximum tolerated dose (MTD) of CIML NK at starting dose level 0. * Screening and baseline visit with assessments and bone marrow aspirate and biopsy. * Day 0: Standard-of-care conditioning chemotherapy and stem cell infusion. * Day 7: Predetermined dose of CIML NK cells 1x daily. * Days 7, 9, 11, 13, 15: Predetermined dose of Interleukin-2 1x daily every other day (5 doses total). * Dose limiting toxicity period for 6 weeks after infusion of CIML NK cells If 0 or 1 dose limiting toxicity is observed at the dose level, then this dose will be the MTD and study will proceed to Phase 1b. De-escalation to dose level -1 per protocol if ≥2 DLTs occur with dose Level 0. In phase Ib, 10 additional participants will be enrolled at the maximum tolerated dose.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity (DLT) [Phase 1] 6 weeks All DLT was defined as an adverse event (AE) that is related to the CIML NK cell infusion combined with IL-2 in adult patients undergoing RIC HLA-matched related or haploidentical donor stem cell transplantation using PTCY-based GVHD prophylaxis. Toxicities are to be assessed according to the CTCAEv5 (Appendix C). Management and dose modifications associated with the above adverse events are outlined in protocol 6.
- Secondary Outcome Measures
Name Time Method Measurable Residual Disease (MRD) Rate At 35 and 100 days MRD rate is defined as the proportion pf participants achieving MRD using the validated NGS-based assay.
1-year Progression-Free Survival (PFS) Rate 1 year 1-year PFS is a probability estimated using progression-free survival based on the Kaplan-Meier method is defined as the duration between randomization and documented disease progression (PD) or death, or is censored at time of last disease assessment.
6-month Graft-versus-host Disease (GVHD) and Relapse Free Survival (GRFS) 6 months 6-month GRFS is a probability estimated using the Kaplan-Meier method. GVHD-free relapse-free survival (GRFS) is defined as grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. GVHD assessment detail in protocol appendix G.
Complete Remission (CR/CRi) Rate (CRR) 100 days The CRR is defined as the proportion of participants achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) based on criteria defined in protocol appendix H.
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.
6-month Acute GVHD Rates 6 months Acute GVHD will be estimated in the competing risks framework treating death or relapse without developing GVHD as a competing event. GVHD assessment detail in protocol appendix G.
100-day Acute GVHD Rates 100 days Acute GVHD will be estimated in the competing risks framework treating death or relapse without developing GVHD as a competing event. GVHD assessment detail in protocol appendix G.
12-month Chronic GVHD Rates 12 months Chronic GVHD will be estimated in the competing risks framework treating death or relapse without developing GVHD as a competing event. GVHD assessment detail in protocol appendix G.
Maximum Tolerated Dose (MTD) [Phase 1] 6 weeks The MTD in the CIML NK cell infusion combined with IL-2 in adult patients undergoing RIC HLA-matched related or haploidentical donor stem cell transplantation using PTCY-based GVHD prophylaxis is determined by the number pf patients who experience a DLT. See previous primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than 2 out of 5 patient in each dose cohort experience a DLT. Dose-de-escalation will take place if MTD considered exceeded in each dose cohort.
12-month Graft-versus-host Disease (GVHD) and Relapse Free Survival (GRFS) 12 months 12-month GRFS is a probability estimated using the Kaplan-Meier method. GVHD-free relapse-free survival (GRFS) is defined as grade 3-4 acute GVHD, chronic GVHD requiring systemic treatment, relapse, or death. GVHD assessment detail in protocol appendix G.
Trial Locations
- Locations (2)
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States