Description:
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).
Title
- Brief Title: Expanded/Activated Gamma Delta T-cell Infusion Following Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide
- Official Title: Phase I Study of Ex Vivo Expanded/Activated Gamma Delta T-cell Infusion Following Haploidentical Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide
Clinical Trial IDs
- ORG STUDY ID:
IIT-2018-Gamma-DeltaTcell
- NCT ID:
NCT03533816
Conditions
- Acute Myeloid Leukemia
- Chronic Myeloid Leukemia
- Acute Lymphoblastic Leukemia
- Myelodysplastic Syndromes
Interventions
| Drug | Synonyms | Arms |
|---|
| EAGD T-cell infusion (Phase I) | CliniMACS-Prodigy, CliniMACS Alpha Beta T-Cell Depletion System | EAGD T-cell infusion (Phase I) |
| EAGD T-cell infusion (Expansion) | CliniMACS-Prodigy, CliniMACS Alpha Beta T-Cell Depletion System | EAGD T-cell infusion (Expansion) |
Purpose
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).
Detailed Description
Many patients with hematological malignancies require a bone marrow transplant for curative
treatment. A matched sibling donor is optimal but may not be available. Therefore, a
partially matched family member (haploidentical) may be a viable alternative. The incidence
of graft vs. host disease, however, can become more of a significant, even fatal, factor with
partial matches.
T-cells have been shown to be the key player in the post-transplant immune phenomena. The
majority of T-cells are composed of alpha beta T-cells with a small minority of gamma delta
T-cells, which are known to have the unique ability to kill malignant cells without antigen
recognition.
This study proposes to extract, concentrate, and activate gamma delta T-cells from the
peripheral blood to provide innate anti-tumor effect with minimal risk of GVHD. Safety and
impact and/or the rate of GVHD will be evaluated.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - 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. | - EAGD T-cell infusion (Expansion)
|
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.
| Maximum Eligible Age: | 65 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Phase I - Dose-limiting toxicity (DLT) |
| Time Frame: | Baseline to Day 30 |
| Safety Issue: | |
| Description: | The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products. |
Secondary Outcome Measures
| Measure: | Expansion phase - Relapse following haploidentical HCT and PTCy with EAGD T-cell infusion |
| Time Frame: | Baseline to 100 days |
| Safety Issue: | |
| Description: | Number of subjects who have acute GVHD by day 100 post-HCT after infusion of EAGD T-cells |
| Measure: | Expansion phase - Non-relapse mortality following haploidentical HCT and PTCy with EAGD T-cell infusion |
| Time Frame: | Baseline to 100 days |
| Safety Issue: | |
| Description: | Number of subjects who have no relapse by day 100 post-HCT after infusion |
| Measure: | Expansion phase - Overall survival following haploidentical HCT and PTCy with EAGD T-cell infusion |
| Time Frame: | Baseline to 100 days |
| Safety Issue: | |
| Description: | Number of subjects who are living by day 100 post-HCT after infusion |
| Measure: | Rate of one-year relapse-free survival (RFS) |
| Time Frame: | Baseline to one year |
| Safety Issue: | |
| Description: | Number of subjects living without relapse of disease after one year following HCT |
| Measure: | Rate of one-year non-relapse mortality (NRM) |
| Time Frame: | Baseline to one year |
| Safety Issue: | |
| Description: | Number of subjects no longer living but not from disease relapse after one year following HCT |
| Measure: | Rate of one-year overall survival (OS) |
| Time Frame: | Baseline to one year |
| Safety Issue: | |
| Description: | Number of subjects living after one year following HCT |
| Measure: | Proportion of subjects with chronic GVHD at one year |
| Time Frame: | Baseline to one year |
| Safety Issue: | |
| Description: | Number of subjects with chronic GVHD after one year following HCT |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | University of Kansas Medical Center |
Trial 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
Last Updated
March 22, 2021
