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Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT03717480
Recruitment Status : Recruiting
First Posted : October 24, 2018
Last Update Posted : March 12, 2020
Sponsor:
Information provided by (Responsible Party):
Vincent T. Ho, MD, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.

The device used to remove the α/βT cells in this study is:

-CliniMACS® TCR α/β Reagent System


Condition or disease Intervention/treatment Phase
Hematologic Malignancy Device: ClinicMACs Not Applicable

Detailed Description:

Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).

The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.

GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:

  • Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
  • Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.

To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.

In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
Actual Study Start Date : January 21, 2020
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TCR α/β Reagent System
  • The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
  • CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device
Device: ClinicMACs
The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants




Primary Outcome Measures :
  1. Severe acute GVHD-free survival rate [ Time Frame: 100 Days ]
    Participant rate of severe acute GVHD-free survival will be assessed at 100 days post-SCT


Secondary Outcome Measures :
  1. Number of participants with grades II-IV acute GVHD [ Time Frame: 2 years ]
    Grades II-IV acute GVHD will be assessed at 2 years post-SCT.

  2. Number of participants with chronic GVHD [ Time Frame: 2 years ]
    Number of participants with chronic GVHD will be assessed at 2 years post-SCT.

  3. Number of participants with GVHD and relapse free survival (GRFS) [ Time Frame: 2 years ]
    GRFS will be defined as alive without having experienced grade 3-4 acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.

  4. Number of participants with immunosuppression-free survival [ Time Frame: 2 years ]
    Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.

  5. Number of participants with hematologic recovery [ Time Frame: 2 years ]
    Hematologic recovery will be assessed in participants at 2 years post-SCT.

  6. Number of participants with immune reconstitution [ Time Frame: 2 years ]
    Immune reconstitution will be assessed in participants at 2 years post-SCT.

  7. Number of participants with disease relapse [ Time Frame: 2 years ]
    Disease relapse will be assessed in participants at 2 years post-SCT.

  8. Number of participants with transplant-related mortality [ Time Frame: 2 years ]
    Participant transplant-related mortality will be assessed at 2 years post-SCT.

  9. Number of participants with organ toxicity [ Time Frame: 2 years ]
    Participant organ toxicity will be assessed at 2 years post-SCT.

  10. Rates of infections [ Time Frame: 2 years ]
    Participant rate of infections will be assessed at 2 years post-SCT.

  11. Number of participants with relapse-free and overall survival [ Time Frame: 2 years ]
    Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Diagnoses and stage at time of transplant admission:

    • Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
    • Myelodysplastic syndromes (MDS) with <10% marrow blasts
    • Myeloproliferative neoplasm (MPN) with <10% marrow blasts
    • CMML with less than 10% marrow blast
    • CML accelerated phase or second or subsequent chronic phase
    • Non-Hodgkin's lymphoma in PR or CR2 or beyond
    • Hodgkin lymphoma in PR or CR2 or beyond
  • Age 18-65 years
  • Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
  • Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
  • Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patient with active HIV infection
  • Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
  • Prior allogeneic hematopoietic stem cell transplantation
  • Impaired cardiac function- ejection fraction < 40%
  • Impaired pulmonary function- pretransplant FEV1, DLCO < 50%
  • Impaired renal function, based on

    --Serum creatinine > 2.0 mg/dl

  • Impaired liver function unrelated to primary disease, based on

    --ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or suspected Gilbert's disease)

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
  • Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
  • Participants with known active CNS disease. CNS disease that has been treated is eligible

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): NCT03717480


Contacts
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Contact: Vincent T Ho, MD 617-632-1943 Vincent_Ho@dfci.harvard.edu

Locations
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United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Vincent T Ho, MD    617-632-1943    Vincent_Ho@dfci.harvard.edu   
Principal Investigator: Vincent T. Ho, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Vincent T Ho, MD Dana-Farber Cancer Institute

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Responsible Party: Vincent T. Ho, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03717480    
Other Study ID Numbers: 18-270
First Posted: October 24, 2018    Key Record Dates
Last Update Posted: March 12, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Vincent T. Ho, MD, Dana-Farber Cancer Institute:
Graft vs. Host Disease
Hematologic Malignancy
Additional relevant MeSH terms:
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Graft vs Host Disease
Neoplasms
Immune System Diseases