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Stem Cell Transplant From Donors After Alpha Beta Cell Depletion in Children and Adults With T-allo10 Cells Addback

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ClinicalTrials.gov Identifier: NCT04640987
Recruitment Status : Not yet recruiting
First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Alice Bertaina, Stanford University

Brief Summary:

The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune reconstitution of the patient while sparing the risk of developing severe Graft-versus-Host Disease (GvHD).

The primary objective of Phase 1 is to determine the recommended Phase 2 dose (RP2D) administered after infusion of αβdepleted-HSCT in children and young adults with hematologic malignancies.

A Phase 1b extension will occur after dose escalation, enrolling at the RP2D for the T-allo10 cells determined in the Phase 1 portion to evaluate the safety and efficacy of infusion of T-allo10 after receipt of αβdepleted-HSCT. Additionally, Phase 1b aims to explore improvements in immune reconstitution.

All participants on this study must be enrolled on another study: NCT04249830


Condition or disease Intervention/treatment Phase
Hematologic Diseases Biological: Allogeneic Stem Cell Transplant Device: CliniMACS Prodigy System Drug: T-allo10 cells addback Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1/1b Study of T-allo10 Infusion After HLA-Partially Matched Related or Unrelated TCR αβ+ T-cell/ CD19+ B-cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation (αβ Depleted-HSCT) in Children and Young Adults Affected by Hematologic Malignancies
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Disorders

Arm Intervention/treatment
Experimental: Experimental: Stem Cell Transplant
The participant will undergo a stem cell transplant using donor cells that have been manipulated through an investigational device. The participant's cells will then be manipulated via a T-allo10 cell addback. Participants will be followed for outcomes for two years.
Biological: Allogeneic Stem Cell Transplant
The allogeneic stem cell transplant involves transferring the stem cells from a healthy person (donor) to the participant via infusion.

Device: CliniMACS Prodigy System
Device used for production of T-allo10 cells.

Drug: T-allo10 cells addback
T-allo10 cells are made by manipulating the participant's stem cell donor's white blood cells (CD4+ T cells) in the presence of their (participant's) CD14+ monocytes.




Primary Outcome Measures :
  1. Number of participants with myeloid engraftment after T-allo10 [ Time Frame: Through day 35 (+/- 7 days) after αβdepleted-HSCT ]
  2. Number of participants without grade II aGvHD requiring steroids after T-allo10 [ Time Frame: Through day 35 (+/- 7 days) after αβdepleted-HSCT ]
  3. Number of participants without grade III/IV aGvHD after T-allo10 [ Time Frame: Through day 35 (+/- 7 days) after αβdepleted-HSCT ]
  4. Number of participants with absence of dose-limiting toxicity (DLT) 28 days following the infusion of T-allo10 given at the recommended phase 2 dose (RP2D) [ Time Frame: Assessed at 28 days (after infusion of T-allo10) ]
  5. Number of participants who reach immune reconstitution (IR) threshold [ Time Frame: Through Day 60 (+/- 10 days) after infusion of T-allo10 ]
    IR (a surrogate of reduced risk of leukemia recurrence) is defined reaching the threshold of 50CD3+CD4+T-cells/µl by Day+60(+/-10days).


Secondary Outcome Measures :
  1. Number of participants with ≥grade 3 adverse event related to T-allo10 infusion [ Time Frame: Through 1 year after αβdepleted-HSCT ]
  2. Number of participants with grade II-IV aGvHD [ Time Frame: Assessed at day 90 after αβdepleted-HSCT ]
  3. Number of participants with grade III-IV aGvHD [ Time Frame: Assessed at day 180 after αβdepleted-HSCT ]
  4. Number of participants with cGvHD [ Time Frame: Assessed at 1 year after αβdepleted-HSCT ]
  5. Leukemia-free survival [ Time Frame: Assessed at 1 year after αβdepleted-HSCT ]
    Leukemia-free survival defined as at the time of enrollment to disease relapse or death from any cause.

  6. Number of participants with disease relapse [ Time Frame: Assessed at 1 year after αβdepleted-HSCT ]
    Disease relapse is defined as the return of signs and symptoms of a disease after a remission.

  7. Non-relapse mortality [ Time Frame: Assessed at Day 90 after αβdepleted-HSCT ]
  8. Non-relapse mortality [ Time Frame: Assessed at 1 year after αβdepleted-HSCT ]


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Ages Eligible for Study:   1 Month to 45 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria prior to enrollment:

  • 1. Age > 1 months (with minimum weight of 10 Kg) and < 45 years.
  • 2. Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830
  • 3. Patients with life-threatening hematological malignancies for which HSCT has been recommended:

    1. High-risk ALL in 1st CR, ALL in 2nd or subsequent CR;
    2. High-risk AML in 1st CR, AML in 2nd or subsequent CR;
    3. Myelodysplastic syndrome;
    4. JMML (Juvenile myelomonocytic leukemia);
    5. Non-Hodgkin lymphomas in 2nd or subsequent CR;
    6. Other hematologic malignancies eligible for stem cell transplantation per institutional standard.
  • 4. All subjects ≥ 18 years of age must be able to give informed consent, or adults lacking capacity to consent must have a LAR available to provide consent. For subjects <18 years old their LAR (i.e. parent or guardian) must give informed consent. Pediatric subjects will be included in age appropriate discussion and verbal assent will be obtained for those > 7 years of age, when appropriate.

Inclusion criteria prior to T-allo10 infusion:

  1. Patient already received αβdepleted-HSCT and has myeloid engraftment.
  2. Absence of active grade II aGvHD requiring >0.5 mg/Kg of steroids or any diagnosis of grade III/IVaGvHD.

Exclusion Criteria prior to MNC collection for Tallo-10 manufacturing.:

  1. Not eligible to receive HSCT on NCT04249830
  2. Received another investigational agent within 30 days of enrollment.
  3. Pregnancy (positive serum or urine beta-HCG) within 7 days of MNC donation.
  4. Patient or donor is not willing or able to undergo an additional non-mobilized apheresis for collection of MNC prior to donation of cells for participation in NCT04249830.

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): NCT04640987


Locations
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United States, California
Lucile Packard Children's Hospital
Palo Alto, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
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Principal Investigator: Alice Bertaina, MD, PhD Associate Professor of Pediatrics, Stem Cell Transplantation
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Responsible Party: Alice Bertaina, Associate Professor of Pediatrics, Stanford University
ClinicalTrials.gov Identifier: NCT04640987    
Other Study ID Numbers: IRB-58549
BMT 367 - T-allo10 Alpha Beta ( Other Identifier: Stanford University )
First Posted: November 23, 2020    Key Record Dates
Last Update Posted: November 23, 2020
Last Verified: November 2020
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: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Hematologic Diseases