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Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02786485
Recruitment Status : Withdrawn
First Posted : June 1, 2016
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 26, 2016
First Posted Date  ICMJE June 1, 2016
Last Update Posted Date October 5, 2020
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2016)
Adverse events [ Time Frame: 30 days after last dose of study drug (BPX-501 and/or rimiducid) ]
Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT
Official Title  ICMJE A Phase I Study of Matched Unrelated Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant
Brief Summary This is a Phase I, multicenter, open-label, non-randomized study of matched unrelated donor BPX-501 T cell infusion in adult subjects with hematological malignancies presenting with recurrent disease minimal residual disease (MRD) post-allogeneic transplant.
Detailed Description Un-manipulated donor lymphocyte infusion (DLI) is used after stem cell transplantation to treat and prevent relapse, to prevent infections and to establish full donor chimerism. The addition of mature T cells which exhibit a broad repertoire of T cell immunity against viral antigens, as well as against cancer antigens, might provide a clinical benefit. However, an expected side effect of the presence of mature T cells is the potential occurrence of acute graft-versus-host disease (aGvHD). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve higher clinical response rate with lower GvHD occurrence. Optimization of DLI dose and schedule as well as strategies of donor T-cell manipulation may lead to the consistent ability to separate GvHD from graft-versus-tumor (GvT) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults and children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Myelodysplastic Syndromes
  • Lymphomas
  • Multiple Myeloma
  • Other High-risk Hematological Malignancies
Intervention  ICMJE
  • Biological: rivogenlecleucel
    T cells transduced with iCasp safety switch
    Other Name: BPX-501
  • Drug: Rimiducid
    administered to treat GVHD
    Other Name: AP1903
Study Arms  ICMJE Experimental: Rivogenlecleucel & Rimiducid

All subjects will receive 3 courses of rivogenlecleucel (BPX-501 T cells) infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0 and DL2 on Days 30 and 60.

Escalating doses of rimiducid (AP1903) (0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after rivogenlecleucel infusion.

Interventions:
  • Biological: rivogenlecleucel
  • Drug: Rimiducid
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 30, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: May 31, 2016)
24
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects aged ≥ 18 yrs and ≤ 65 yrs;
  • Clinical diagnosis of one of the following hematological malignancies:

    • Leukemia
    • Myelodysplastic Syndromes
    • Lymphomas
    • Multiple Myeloma
    • Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard;
  • Recurrent disease that presents ≥100 days after, or minimal residual disease (MRD) that presents ≥ 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP);
  • Life expectancy >10 weeks;
  • Signed donor and patient/guardian informed consent;
  • A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1;
  • Performance status: Karnofsky score > 50%;
  • Subjects with adequate organ function as measured by:

    • Bone marrow:

      • > 25% donor T-cell chimerism post-transplant
      • Absolute neutrophil count (ANC) >1 x 109/L
    • Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 45%
    • Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) ≥ 50% predicted (corrected for hemoglobin)
    • Hepatic: direct bilirubin ≤ 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5x ULN
    • Renal: creatinine ≤ 2x of ULN for age.

Exclusion Criteria:

  • ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening;
  • Active central nervous system (CNS) involvement with malignant cells (≤ 2 months prior to consenting);
  • Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the principal investigator is the final arbiter of this criterion;
  • Positive HIV serology or viral RNA;
  • Pregnancy (positive serum β human chorionic gonadotropin [HCG] test) or breast-feeding;
  • Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation;
  • Bovine product allergy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT02786485
Other Study ID Numbers  ICMJE BP-008-MUD
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bellicum Pharmaceuticals
Study Sponsor  ICMJE Bellicum Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bellicum Pharmaceuticals Bellicum Pharmaceuticals, Inc.
PRS Account Bellicum Pharmaceuticals
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP