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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. Identifier: NCT02786485
Recruitment Status : Withdrawn
First Posted : June 1, 2016
Last Update Posted : October 5, 2020
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Leukemia Myelodysplastic Syndromes Lymphomas Multiple Myeloma Other High-risk Hematological Malignancies Biological: rivogenlecleucel Drug: Rimiducid Phase 1

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 2016
Actual Primary Completion Date : December 2018
Actual Study Completion Date : December 2018

Arm Intervention/treatment
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.

Biological: rivogenlecleucel
T cells transduced with iCasp safety switch
Other Name: BPX-501

Drug: Rimiducid
administered to treat GVHD
Other Name: AP1903

Primary Outcome Measures :
  1. 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

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

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.

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 identifier (NCT number): NCT02786485

Sponsors and Collaborators
Bellicum Pharmaceuticals
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Study Director: Bellicum Pharmaceuticals Bellicum Pharmaceuticals, Inc.
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Responsible Party: Bellicum Pharmaceuticals Identifier: NCT02786485    
Other Study ID Numbers: BP-008-MUD
First Posted: June 1, 2016    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 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: No
Keywords provided by Bellicum Pharmaceuticals:
Hematological malignancies
Hematologic diseases
Leukemias and Myelodysplastic Syndromes
Multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Hematologic Neoplasms
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Neoplasms by Site