Expanded/activated gamma delta T-cell infusions after haploidentical stem cell transplant with post-transplant cyclophosphamide.

Phase I Study of Ex Vivo Expanded/Activated Gamma Delta T-cell Infusion Following Haploidentical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

This tests whether infusing expanded/activated gamma delta T cells after a partially matched (haploidentical) stem cell transplant with post-transplant cyclophosphamide helps control leukemia and reduce graft-versus-host disease in adults.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 38 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of Kansas Medical Center (other)
• Locations: 2 sites (Westwood, Kansas and 1 other locations)
• Trial ID: NCT03533816 on ClinicalTrials.gov

What this trial studies

This Phase 1 trial collects peripheral blood gamma delta T cells from donors, expands and activates them outside the body, and infuses the product into patients who receive a haploidentical hematopoietic stem cell transplant with post-transplant cyclophosphamide. The primary focus is safety and the rate of graft-versus-host disease after infusion, with secondary observation of anti-tumor activity. Eligible patients include adults with AML, ALL, CML, or intermediate/high-risk MDS undergoing a partially matched family-donor transplant. The intervention is given in the early post-transplant period and participants are followed for transplant-related outcomes and adverse events.

Who should consider this trial

Good fit: Adults aged 19–65 with AML, ALL, CML, or intermediate/high‑risk MDS who are planning a haploidentical allogeneic stem cell transplant with post‑transplant cyclophosphamide and meet organ-function and donor‑antibody criteria are ideal candidates.

Not a fit: Patients with a fully matched donor, those outside the 19–65 age range, those with significant organ dysfunction or uncontrolled infection, or those with positive donor‑specific antibodies may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could lower relapse rates and reduce graft-versus-host disease, making haploidentical transplants safer and more effective.

How similar studies have performed: Preclinical studies and early-phase clinical work with gamma delta T-cell therapies have shown anti-tumor activity, but clinical evidence for expanded gamma delta T cells specifically after haploidentical transplant with PTCy is limited.

Eligibility criteria

Inclusion Criteria:

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.
* Consent: All patients must be informed of the investigational nature of this study and given written informed consent in accordance with institutional and federal guidelines.

The following criteria are required within 48 hours prior to infusion of the EAGD T cell product.

* Absence of uncontrolled infection with sepsis syndrome (e.g persistent positive blood culture).
* NO hemodynamic instability (due to sepsis or organ dysfunction) or circulatory volume overload.
* NO clinically significant organ toxicity that are defined as follows:

  * Heart failure with subnormal LVEF or clinical fluid overload.
  * Elevated serum creatinine or subnormal creatinine clearance (either estimated or measured).
  * Elevated total bilirubin ≥1.5 upper normal level (unless indirect hyperbilirubinemia attributed to non-hepatic pathology), or elevated liver enzymes (ALT, AST, ALP) \>5 x ULN.
  * Hypoxemia requiring oxygen therapy
* NO acute graft versus host disease (any grade).
* Neutrophil engraftment.

Exclusion Criteria:

* 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.

Where this trial is running

Westwood, Kansas and 1 other locations

• University of Kansas Cancer Center — Westwood, Kansas, United States (RECRUITING)
• Ohio State University Medical Center — Columbus, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Joseph McGuirk, M.D. — University of Kansas Medical Center
• Study coordinator: Clinical Trial Nurse Navigator

Conditions: Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Gamma delta T-cells, Hematopoietic Stem Cell Transplantation, Post-transplant Cyclophosphamide, Expanded/Activated gamma delta