Clinical Trials /

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

NCT02477878

Description:

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.

Related Conditions:
  • Hematopoietic and Lymphoid Malignancy
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant
  • Official Title: A Phase I Study of Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant

Clinical Trial IDs

  • ORG STUDY ID: BP-008
  • NCT ID: NCT02477878

Conditions

  • Leukemia
  • Myelodysplastic Syndromes
  • Lymphoma
  • Multiple Myeloma
  • Hematologic Neoplasms

Interventions

DrugSynonymsArms
BPX-501BPX-501 and AP1903
AP1903RimiducidBPX-501 and AP1903

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
BPX-501 and AP1903ExperimentalAll 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.
  • BPX-501
  • AP1903

Eligibility Criteria

        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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events
Time Frame:1 year
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Response Rate
Time Frame:2 years
Safety Issue:
Description:Measure overall survival and disease free survival 2 years after BPX-501 infusion

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Bellicum Pharmaceuticals

Trial Keywords

  • Adult leukemias and myelodysplasia
  • Adult lymphomas
  • Adult multiple myeloma
  • allogeneic stem cell transplant
  • donor lymphocyte infusion

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