Expanded/Activated Gamma Delta T-cell Infusion Following Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

NCT03533816 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IIT-2018-Gamma-DeltaTcell
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

Gamma delta T-cells are part of the innate immune system with the ability to recognize malignant cells and kill them. This study uses gamma delta T-cells to maximize the anti-tumor response and minimize graft versus host disease (GVHD) in leukemic and myelodysplastic patients who have had a partially mismatched bone marrow transplant (haploidentical).

Conditions

Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes

Keywords

Gamma delta T-cells; Hematopoietic Stem Cell Transplantation (HCT); Post-transplant Cyclophosphamide (PTCy); Expanded/Activated gamma delta (EAGD); Graft versus host disease (GVHD); haploidentical

Outcome Measures

Primary Outcomes (3)

• Phase I - Dose-limiting toxicity (DLT)

  The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products.

  Baseline to Day 30

• Phase I - Severe acute adverse events following infusion of EAGD T-cells

  Safety of the infusion will be based on the risk of treatment-related severe adverse events as identified in the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 4.

  Baseline to Day 100

• Expansion phase - Rate of acute GVHD

  Monitoring for GVHD is assessed with Grade II-IV adverse events as identified by the National Cancer Common Terminology Criteria for Adverse Events (CTCAE) version 4.

  Baseline to Day 100

Secondary Outcomes (7)

• Expansion phase - Relapse following haploidentical HCT and PTCy with EAGD T-cell infusion

  Baseline to 100 days

• Expansion phase - Non-relapse mortality following haploidentical HCT and PTCy with EAGD T-cell infusion

  Baseline to 100 days

• Expansion phase - Overall survival following haploidentical HCT and PTCy with EAGD T-cell infusion

  Baseline to 100 days

• Rate of one-year relapse-free survival (RFS)

  Baseline to one year

• Rate of one-year non-relapse mortality (NRM)

  Baseline to one year

Study Arms (2)

EAGD T-cell infusion (Phase I)

EXPERIMENTAL

Peripheral blood is collected by leukapheresis from the donor, expanded and activated on CliniMACS-Prodigy, further depleted of alpha beta T-cells using the CliniMACS Alpha Beta T-Cell Depletion System, which leaves a gamma delta T-cell rich product. This product is then infused into the recipient at either 1, 3, or 10 x 1,000,000 cells/kg concentrations depending upon the cohort.

Drug: EAGD T-cell infusion (Phase I)

EAGD T-cell infusion (Expansion)

EXPERIMENTAL

Peripheral blood is collected by leukapheresis from the donor, expanded and activated on CliniMACS-Prodigy, further depleted of alpha beta T-cells using the CliniMACS Alpha Beta T-Cell Depletion System, which leaves a gamma delta T-cell rich product. This product is then infused into the recipient at the maximum tolerated dose as determined from Phase I.

Drug: EAGD T-cell infusion (Expansion)

Interventions

EAGD T-cell infusion (Phase I) DRUG

The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.

Also known as: CliniMACS-Prodigy, CliniMACS Alpha Beta T-Cell Depletion System

EAGD T-cell infusion (Phase I)

EAGD T-cell infusion (Expansion) DRUG

The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.

Also known as: CliniMACS-Prodigy, CliniMACS Alpha Beta T-Cell Depletion System

EAGD T-cell infusion (Expansion)

Eligibility Criteria

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

You may qualify if:

• The following criteria are used to enroll patients in the study before transplant.
• Patients with neoplastic hematological disorders with indication of allogeneic transplant according to the National Comprehensive Cancer Network (NCCN) or other standard guidelines as follows:
• Acute myeloid leukemia \[AML\] in morphologic complete remission with intermediate/high-risk features (per NCCN criteria) or relapsed disease
• Chronic myeloid leukemia \[CML\] in any chronic phase.
• Myelodysplastic syndrome \[MDS\] with intermediate/high risk features or refractory disease (with bone marrow blast count \<10%).
• Acute lymphoblastic leukemia \[ALL\] in morphologic complete remission with high-risk features or relapsed disease.
• Negative test for donor-specific antibody within 28 days of starting conditioning regimen.
• Age Criteria: 19-65 years.
• Organ Function Criteria: The following organ function testing should be done within 35 days before study registration.
• Cardiac: Normal left ventricular ejection fraction (LVEF) (50% or above) as measured by MUGA or Echocardiogram.
• Pulmonary: FVC, FEV1 and DLCO (corrected) should be 50% or above of expected.
• Renal: serum creatinine level to be \<2 mg/dl AND estimated (Cockcroft-Gault formula) or measured (takes priority if done) creatinine clearance (CrCl) must be equal or greater than 70 mL/min/1.73 m2.
• Hepatic: serum bilirubin 1.5 upper limit of normal (ULN), Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN, and alkaline phosphatase 2.5 ULN.
• Performance status: Karnofsky performance score (KPS) or Lansky score: ≥80.
• Hematopoietic cell transplant comorbidity index (HCT-CI) \<3. Exception may be made on individual cases after discussion with the primary investigator.

You may not qualify if:

• Non-compliant patients.
• No appropriate caregivers identified.
• Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician).
• Active central nervous system (CNS) neoplastic involvement.
• Morbid obesity with body mass index \>35 (borderline cases may be considered on case-by-case basis after discussion with the primary investigator).
• Patients with known allergy to DMSO.
• HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• In8bio Inc.: collaborator

Study Sites (2)

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

Ohio State University Medical Center

Columbus, Ohio, 43210-1238, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Graft vs Host Disease

Interventions

Clinical Trials, Phase I as Topic

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Joseph McGuirk, M.D.

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Nurse Navigator

CONTACT

913-945-7552; ctnursenav@kumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor & Division Director

Model Details: This dose escalation study will be conducted in two phases. The first phase will have three cohorts with three recipient/donor pairs at different dose levels for each cohort. The second phase is an expansion cohort at the maximum tolerated dose determined in the first phase.

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 23, 2018
• Study Start: January 31, 2020
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)