Cytokine-Induced Memory-Like Natural Killer Cells (CIML-NK) for Relapsed & Refractory Acute Myeloid Leukemia (AML)

NCT ID: NCT05580601

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-05
• Study Completion Date: 2027-07-31

Brief Summary

The objective of this study is to demonstrate that cytokine-induced memory-like natural killer cells can be generated from donor cells and infused safely into patients with relapsed or refractory acute myeloid leukemia (AML). A secondary objective is to assess efficacy of the CIML-NK cells in treating AML.

Detailed Description

The goal of treatment of relapsed or refractory acute myeloid leukemia (AML) is to achieve remission and proceed to hematopoietic stem cell transplant (HSCT). Unfortunately, standard protocols have limited success. In this study the investigators will identify patients with relapsed or refractory AML who are unlikely to benefit from standard chemotherapy protocols and do not qualify for, or do not wish to participate in, institutional chemotherapy trials. Peripheral blood from a related haploidentical donor will be collected for the isolation of natural killer (NK) cells. NK cells will be induced into a memory-like state using cytokine supplementation only. In this Phase I/II study, Patients will receive a lymphodepleting chemotherapy regimen, after which the cytokine-induced memory-like NK cells (CIML-NKs) will be infused. The primary study endpoint is the feasibility and safety of infusion of the cells. The secondary endpoints are efficacy, as measured by clinical response per standard CR/CRi criteria and ability to subsequently undergo allogeneic HSCT, and the persistence of memory-like NK cells in the blood as measured by flow cytometry.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cytokine-Induced Memory-Like Natural Killer (CIML-NK) Cells

The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product.

Group Type: EXPERIMENTAL

CIML-NK Cells

Intervention Type: DRUG

The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product. At the time of infusion, the product is comprised of:

• Cytokine-Induced Memory-Like NK cells (CIML-NK cells)
• Human Serum Albumin
• Plasmalyte

The concentration and total cell number of CIML-NK cells in the product will vary based on the recipient body weight and the dose requested.

Interventions

CIML-NK Cells

The investigational cell product is a cytokine-induced memory-like natural killer cell preparation, derived from the recipient's haploidentical donor's apheresis product. At the time of infusion, the product is comprised of:

• Cytokine-Induced Memory-Like NK cells (CIML-NK cells)
• Human Serum Albumin
• Plasmalyte

The concentration and total cell number of CIML-NK cells in the product will vary based on the recipient body weight and the dose requested.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Of age ≥ 2 years of age at the time of study enrollment
• With AML diagnosed per 2016 WHO criteria (11)
• With relapsed or refractory AML in their bone marrow
• Refractory disease: Patients must have ≥ 5% blasts in the bone marrow after 2 courses of intensive induction treatment
• Relapsed disease: Patients must have ≥ 5% blasts in the bone marrow, or reappearance of blasts in the blood, within 6 months of initial CR
• With available haploidentical related donors. Donor specific antibody (DSA) testing will be done on the recipient prior to or upon enrollment.
• With performance level of ≥ 50% on Karnofsky scale for patients > 16 years of age and ≥ 50% on Lansky scale for patients ≤ 16 years of age

Exclusion Criteria

• Disease: isolated central nervous system (CNS) disease, or isolated extramedullary disease, or diagnosis of acute promyelocytic leukemia (APML). Patients with extramedullary disease in combination with bone marrow disease are eligible for enrollment.
• Infectious Disease: Active uncontrolled infection
• Cardiac function: Systolic ejection fraction <45% by echocardiogram
• Pulmonary Function: Oxygen saturation <92% on room air
• Hepatic function: Total bilirubin > 2mg/dL, AST and ALT more than three times the upper limit of normal
• Concomitant medications: receiving either >10mg prednisone equivalent daily, or >0.5mg/kg prednisone equivalent daily, whichever is less
• Concomitant investigational treatments: receiving other investigational therapies
• Known allergy or hypersensitivity reaction to IL-2 injections
• Pregnant or breastfeeding women will not be entered on this study due to risks of fetal and teratogenic adverse events with lymphodepleting chemotherapy. Pregnancy tests must be obtained for female patients. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion. Effective contraceptive methods include oral contraceptive pills, patches, or injections, intrauterine devices, having a tubal ligation, having a partner who has had a vasectomy, or not having sex.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zahra Hudda

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Medical Center, Cincinnati

Locations

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Zahra Hudda

Role: CONTACT

Zahra.Hudda@cchmc.org

917-754-7118

Caitlin Cottrell

Role: CONTACT

Caitlin.cottrell@cchmc.org

513-803-7039

Facility Contacts

Caitlin Cottrell

Role: primary

Caitlin.cottrell@cchmc.org

Richard Cooper

Role: backup

richard.cooper@cchmc.org

Other Identifiers

2020-0853

Identifier Type: -

Identifier Source: org_study_id