Safety Study of Gene Modified Donor T-cells Following TCR Alpha Beta Depleted Stem Cell Transplant

Sponsor
Bellicum Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02065869
Collaborator
(none)
193
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226.1
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Study Details

Study Description

Brief Summary

This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (Graft versus host disease).

Detailed Description

This is a Phase II extension study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration severe acute graft versus host disease (GvHD).

The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment.

Study Design

Study Type:
Interventional
Actual Enrollment :
193 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Extension Study of CaspaCIDe T Cells (BPX-501) From an HLA-partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders
Actual Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Jan 30, 2020
Anticipated Study Completion Date :
Feb 1, 2033

Arms and Interventions

Arm Intervention/Treatment
Experimental: BPX-501 T cells and rimiducid

TCR alpha beta depleted graft infusion with addback of BPX-501 T cells (rivogenlecleucel). Rimiducid/AP1903: Dimerizer drug administered to subjects who develop Grade III-IV acute GVHD, Grade II gut/liver acute GVDH or Grade I/II skin-only acute GvHD which is non-responsive after 7 days of standard of care treatment

Biological: BPX-501 T cells
1x10E6 cells/kg infused on Day 0
Other Names:
  • rivogenlecleucel
  • Drug: rimiducid
    0.4mg/kg administered IV to treat GVHD
    Other Names:
  • AP1903
  • Outcome Measures

    Primary Outcome Measures

    1. Event-Free -Survival [180 days after transplant]

      events include TRM (or NRM for malignant patients), severe GVHD (acute Grade 2-4 organ or extensive chronic GVHD) and life threatening infections (Grade 4)

    Secondary Outcome Measures

    1. TRM (non-malignant) or NRM (malignant) [180 days after transplant]

      transplant related mortality or non relapse mortality (patients with malignant disease)

    2. Cumulative incidence and severity of acute (grade 2-4) and chronic GvHD at 180 days [180 days after transplant]

      grades 2-4 acute and chronic GvHD

    3. Time to resolution of acute GvHD after administration of rimiducid [180 days after transplant]

      resolution of acute GvHD

    4. Immune reconstitution [180 days after transplant]

      absolute CD3, CD4 and CD8 count

    5. Disease free/cGvHD [180 days after transplant]

      Disease free/cGvHD survival

    6. Disease status [180 days after transplant]

      Disease status of each specific disease indication

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Month to 18 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age < 18 years and > 1 month (< 1 month upon approval by Sponsor)

    • Life expectancy > 10 weeks

    • Patients deemed clinically eligible for allogeneic stem cell transplantation.

    • Patients may have failed prior allograft

    • Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.

    • Non-malignant disorders deemed curable by allogeneic transplantation: a. primary immune deficiencies, b. severe aplastic anemia not responding to immune suppressive therapy, c. osteopetrosis d. selected cases of erythroid disorders such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia.

    1. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML).

    Note: Subjects will be eligible if they meet either item 5 OR item 6.

    • Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically identical relative or 10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor

    • A minimum genotypic identical match of 5/10 is required.

    • The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1.

    • Lansky/Karnofsky score > 50

    • Signed informed consent by the patient or the patient's parent or guardian for patients who are minors

    Exclusion Criteria:
    • Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening

    • Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening

    • Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance <30ml/min/1.73m2)

    • Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)

    • Current clinically active infectious disease (including positive HIV serology or viral RNA)

    • Serious concurrent uncontrolled medical disorder

    • Pregnant or breast feeding female patient

    • Lack of parents'/guardian's informed consent for children who are minors.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 IRCCS Ospedale Pediatrico Bambino Gesù Roma Italy 00161
    2 Royal Free London NHS Foundation Trust London United Kingdom NW3 2QG
    3 Institute of Child Health & Great Ormond Street Hospital London United Kingdom WC1N 1EH
    4 Great North Children's Hospital Newcastle Upon Tyne United Kingdom NE1 4LP

    Sponsors and Collaborators

    • Bellicum Pharmaceuticals

    Investigators

    • Study Director: Bellicum Pharmaceuticals, Bellicum Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bellicum Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02065869
    Other Study ID Numbers:
    • BP-004
    First Posted:
    Feb 19, 2014
    Last Update Posted:
    Jul 12, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bellicum Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 12, 2022