Preemptive CIML NK Cell Therapy After Hematopoietic Stem Cell Transplantation

NCT06138587 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 23-535
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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)

Conditions

Leukemia; Acute Myeloid Leukemia; Leukemia, Myeloid; Myelodysplastic Syndromes; Myeloproliferative Neoplasm; Myeloproliferative Disorders

Keywords

Acute Myeloid Leukemia; Leukemia; Leukemia, Myeloid; Myelodysplastic Syndrome; MDS and Myeloproliferative Neoplasm Overlap Syndrome

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity (DLT) [Phase 1]

  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.

  6 weeks

Secondary Outcomes (10)

• Maximum Tolerated Dose (MTD) [Phase 1]

  6 weeks

• Complete Remission (CR/CRi) Rate (CRR)

  100 days

• Measurable Residual Disease (MRD) Rate

  At 35 and 100 days

• 1-year Progression-Free Survival (PFS) Rate

  1 year

• 1-year Overall Survival (OS)

  1 year

Study Arms (1)

Phase 1/1b: CIML NK Cells + Interleukin-2

EXPERIMENTAL

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.

Biological: Cytokine Induced Memory-like Natural Killer Cells; Biological: Interleukin-2

Interventions

Cytokine Induced Memory-like Natural Killer Cells BIOLOGICAL

Allogeneic, cytokine induced memory-like natural killer cells, via intravenous infusion per protocol.

Also known as: CIML NK cells

Phase 1/1b: CIML NK Cells + Interleukin-2

Interleukin-2 BIOLOGICAL

Recombinant, human glycoprotein, single-use 22 MIU vials, via subcutaneous injection per protocol.

Also known as: Aldesleukin, Proleukin

Phase 1/1b: CIML NK Cells + Interleukin-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of AML, MDS, or MDS/MPN that is at high risk for post-transplant relapse and that has measurable disease prior to transplant, except for patients with TP 53 mutated disease who are eligible regardless of measurable residual disease. Patients at high risk for post-transplant relapse include:
• De novo AML diagnosed at or after age 60, except CBF AML
• De novo AML in CR1 AND MRD+ by Hematologics Inc. flow cytometry pretransplant (this would be on the most recent pre-transplant bone marrow)
• Secondary AML
• Any AML transplanted in CR2 or greater
• TP53-mutated MDS or AML
• Therapy-related MDS or AML
• MDS with monosomy 7
• MDS with \>= 10% blasts at the time of transplant
• MDS/MPN or CMML
• Adequate organ function within 2 weeks of NK cell infusion as defined below (should correspond with admission for SCT):
• Total 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
• Serum creatinine \</= 2.0mg/dL
• O2 saturation: ≥90% on room air

You may not qualify if:

• Adult participants who are eligible for and who would be expected to have a greater benefit from myeloablative conditioning in their SOC allo HSCT as judged by their treating physician
• Participants with mutations such as FLT3-ITD, IDH, or BCR-ABL mutations who are planned to receive targeted agent maintenance therapy to prevent relapse post-transplant are excluded.
• Extramedullary leukemia involving sanctuary sites not readily accessible to immune surveillance, such as CNS or testis. Other sites of extramedullary relapse (e.g., leukemia cutis, granulocytic sarcoma) are acceptable.
• Prior history of allogeneic stem cell transplant other than SOC alloHSCT referred to in this study taking place 7 days prior to CIML NK infusion.
• Prior history of solid organ (allograft) transplantation
• Prior history of allergic reactions to cellular products
• Uncontrolled concurrent illness such as ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, or psychiatric/social illness that would limit compliance with study requirements.
• Pregnant women are excluded from this study because of the unknown teratogenic risk of CIML NK cells and IL-2 and with the potential for teratogenic or abortifacient effects by Flu/Cy chemotherapy regimen. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CIML NK cells and IL-2, breastfeeding should be discontinued if the mother is treated on this study.
• HIV-positive patients are excluded due to the potential for interaction between antiretroviral therapy as well as the risk for lethal infection in the context of marrow-suppressive therapy.
• Patients with active and uncontrolled Hepatitis B or C are ineligible due to the high risk of treatment-related hepatotoxicity after cellular therapy.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances: 1. History of other malignancy and have had complete remission of disease for at least 2 years; 2. Diagnosed and treated within the past 2 years for: nonmetastatic melanoma, surgically resected (not needing systemic chemotherapy) squamous cell carcinoma of skin and nonmetastatic prostate cancer not needing systemic chemotherapy.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in study. 3. Diagnosed with MGUS or smoldering myeloma, and/or treated for multiple myeloma or plasmacytoma as long as attainment of complete remission by IMWG criteria following therapy.
• Prior history of Grade 2 or higher hemolytic anemia (\>/= 2g decrease in hemoglobin plus laboratory evidence of hemolysis) from any cause.
• Adequate organ function within 24 hours of NK cell infusion as defined below:
• Total bilirubin: ≤1.5 x institutional upper limit of normal (ULN) (except Gilbert's or disease-related hemolysis, then \< 3 x ULN)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Leukemia, Myeloid; Myelodysplastic Syndromes; Myeloproliferative Disorders

Interventions

Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Roman Shapiro, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roman Shapiro, MD

CONTACT

617-632-3470; roman_shapiro@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: November 18, 2023
• Study Start: January 24, 2024
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)