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Trial record 4 of 4 for:    gamma-delta t cells | leukemia

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

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ClinicalTrials.gov Identifier: NCT03533816
Recruitment Status : Not yet recruiting
First Posted : May 23, 2018
Last Update Posted : September 25, 2019
Sponsor:
Collaborator:
Incysus
Information provided by (Responsible Party):
Joseph McGuirk, University of Kansas Medical Center

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).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Chronic Myeloid Leukemia Acute Lymphoblastic Leukemia Myelodysplastic Syndromes Drug: EAGD T-cell infusion (Phase I) Drug: EAGD T-cell infusion (Expansion) Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 15, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: EAGD T-cell infusion (Phase I)
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)
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
Other Names:
  • CliniMACS-Prodigy
  • CliniMACS Alpha Beta T-Cell Depletion System

Experimental: EAGD T-cell infusion (Expansion)
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)
The Alpha Beta (α/β) T-Cell Depletion System utilizes the CliniMACS instrument to yield a gamma delta (γδ) enriched cell therapy product.
Other Names:
  • CliniMACS-Prodigy
  • CliniMACS Alpha Beta T-Cell Depletion System




Primary Outcome Measures :
  1. Phase I - Dose-limiting toxicity (DLT) [ Time Frame: Baseline to Day 30 ]
    The dose escalation strategy will follow the Food and Drug Administration Guideline for design of early phase clinical trials of cellular therapy products.

  2. Phase I - Severe acute adverse events following infusion of EAGD T-cells [ Time Frame: Baseline to Day 100 ]
    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.

  3. Expansion phase - Rate of acute GVHD [ Time Frame: Baseline to Day 100 ]
    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.


Secondary Outcome Measures :
  1. Expansion phase - Relapse following haploidentical HCT and PTCy with EAGD T-cell infusion [ Time Frame: Baseline to 100 days ]
    Number of subjects who have acute GVHD by day 100 post-HCT after infusion of EAGD T-cells

  2. Expansion phase - Non-relapse mortality following haploidentical HCT and PTCy with EAGD T-cell infusion [ Time Frame: Baseline to 100 days ]
    Number of subjects who have no relapse by day 100 post-HCT after infusion

  3. Expansion phase - Overall survival following haploidentical HCT and PTCy with EAGD T-cell infusion [ Time Frame: Baseline to 100 days ]
    Number of subjects who are living by day 100 post-HCT after infusion

  4. Rate of one-year relapse-free survival (RFS) [ Time Frame: Baseline to one year ]
    Number of subjects living without relapse of disease after one year following HCT

  5. Rate of one-year non-relapse mortality (NRM) [ Time Frame: Baseline to one year ]
    Number of subjects no longer living but not from disease relapse after one year following HCT

  6. Rate of one-year overall survival (OS) [ Time Frame: Baseline to one year ]
    Number of subjects living after one year following HCT

  7. Proportion of subjects with chronic GVHD at one year [ Time Frame: Baseline to one year ]
    Number of subjects with chronic GVHD after one year following HCT



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03533816


Contacts
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Contact: Clinical Trial Nurse Navigator 913-945-7552 ctnursenav@kumc.edu

Locations
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United States, Kansas
University of Kansas Medical Center Not yet recruiting
Westwood, Kansas, United States, 66205
Contact: Clinical Trials Nurse Navigator    913-945-7552    ctnursenav@kumc.edu   
Contact: Joseph McGuirk, M.D.    913-588-6030    jmcguirk@kumc.edu   
Sponsors and Collaborators
University of Kansas Medical Center
Incysus
Investigators
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Principal Investigator: Joseph McGuirk, M.D. University of Kansas Medical Center

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Responsible Party: Joseph McGuirk, Professor & Division Director, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT03533816     History of Changes
Other Study ID Numbers: IIT-2018-Gamma-DeltaTcell
First Posted: May 23, 2018    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joseph McGuirk, University of Kansas Medical Center:
Gamma delta T-cells
Hematopoietic Stem Cell Transplantation (HCT)
Post-transplant Cyclophosphamide (PTCy)
Expanded/Activated gamma delta (EAGD)
Graft versus host disease (GVHD)
haploidentical
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Lymphoid
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists