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Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant

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: NCT02477878
Recruitment Status : Active, not recruiting
First Posted : June 23, 2015
Last Update Posted : October 8, 2019
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 18, 2015
First Posted Date  ICMJE June 23, 2015
Last Update Posted Date October 8, 2019
Actual Study Start Date  ICMJE July 2016
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2018)
  • Adverse events [ Time Frame: 1 year ]
    To evaluate the safety of 2 stratified dose levels of BPX-501 T cell infusions based on patient-donor match in adult subjects with hematological malignancies
  • Adverse events [ Time Frame: 36 hours ]
    evaluate the safety of the infusion of escalating doses of dimerizer drug rimiducid (AP1903) in subjects who develop acute GvHD after BPX-501 infusion
Original Primary Outcome Measures  ICMJE
 (submitted: June 18, 2015)
Adverse events [ Time Frame: 2 years ]
Number of adverse events after BPX-501 as a measure of safety
Change History Complete list of historical versions of study NCT02477878 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2018)
Response Rate [ Time Frame: 2 years ]
Measure overall survival and disease free survival 2 years after BPX-501 infusion
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2015)
Adverse events [ Time Frame: 48 hours ]
Number of adverse events after AP1903 as a measure of safety
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant
Official Title  ICMJE A Phase I Study of Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant
Brief Summary A Phase I study of BPX-501 T cell infusion in adults with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The treatment consists of increasing doses of BPX-501 T cell infusions to achieve a clinical response. AP1903 will be investigated for the treatment of aGvHD after BPX-501 T cell infusion to determine a dose that can mitigate GvHD and preserve the graft versus leukemia effect.
Detailed Description Unmanipulated 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 and 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). BPX-501 contains genetically modified donor T cells that have an inducible safety switch iCasp9 suicide gene. Evidence has emerged that escalating DLI has achieved 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 GvL (graft-versus-leukemia) activity and improve the safety of DLI treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Myelodysplastic Syndromes
  • Lymphoma
  • Multiple Myeloma
  • Hematologic Neoplasms
Intervention  ICMJE
  • Biological: BPX-501
    Biological: T cells transduced with CaspaCIDe suicide gene
  • Drug: AP1903
    AP1903 administered to treat GVHD
    Other Name: Rimiducid
Study Arms  ICMJE Experimental: BPX-501 and AP1903

All subjects will receive 3 cycles of BPX-501 T cell infusions at escalating dose levels (DL). DL1 on Day 0, DL2 on Days 30 and 60. The first dose of BPX-501 T cells will occur ≥30 days after hematopoietic stem cell transplant (HSCT).

Two doses of AP1903 ( 0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion.

  • Biological: BPX-501
  • Drug: AP1903
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 15, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: June 18, 2015)
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects aged >18yrs and < 65yrs
  2. Clinical diagnosis of one of the following adult hematological malignancies

    1. Leukemia
    2. Myelodysplastic Syndromes
    3. Lymphomas
    4. Multiple myeloma
    5. Other high-risk hematologic malignancies eligible for stem cell transplantation per institutional standard Life expectancy >10 weeks
  3. Evidence of recurrent disease that presents > 100 days or minimal residual disease (MRD) that presents > 30 days after one of the following:

    1. Matched related HSCT
    2. Mismatched related HSCT
  4. Signed patient informed consent;
  5. A minimum genotypic identical match of 4/8 is required, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA- DRB1
  6. Performance status: Karnofsky score > 50%
  7. Subjects with adequate organ function as measured by:

    1. Bone marrow:

      • > 25% donor T-cell chimerism
      • ANC >1 x 10E9/L
    2. Cardiac: left ventricular ejection fraction at rest must be >45%.
    3. Hepatic: direct bilirubin ≤ 3 x upper limit of normal, or AST/ALT ≤ 5 x upper limit of normal
    4. Renal: creatinine ≤ 2x of ULN for age
    5. Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin)

Exclusion Criteria:

  1. ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at time of screening;
  2. Active CNS involvement by malignant cells;
  3. 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;
  4. Positive HIV serology or viral RNA
  5. Pregnancy (positive serum βHCG test) or breast-feeding;
  6. Subjects of reproductive potential unwilling to use effective forms of birth control or abstinence for a year after transplantation;
  7. 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 United States
Removed Location Countries Italy
Administrative Information
NCT Number  ICMJE NCT02477878
Other Study ID Numbers  ICMJE BP-008
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bellicum Pharmaceuticals
Study Sponsor  ICMJE Bellicum Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Madhuri Vusirikala, MD University of Texas
PRS Account Bellicum Pharmaceuticals
Verification Date October 2019

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