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

NCT03301168

Description:

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).

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
  • 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

Clinical Trial IDs

  • ORG STUDY ID: BP-U-004
  • NCT ID: NCT03301168

Conditions

  • Acute Lymphoblastic Leukemia
  • Leukemia, Acute Myeloid (AML), Child
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Primary Immune Deficiency Disorder
  • Osteopetrosis
  • Cytopenia
  • Hemoglobinopathy in Children
  • Anemia, Aplastic

Interventions

DrugSynonymsArms
BPX-501 T cellsBPX-501 T cells and AP1903
AP1903rimiducidBPX-501 T cells and AP1903

Purpose

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 2 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 that does not adequately respond
      to standard of care therapy.
    

Trial Arms

NameTypeDescriptionInterventions
BPX-501 T cells and AP1903ExperimentalTCR alpha beta depleted graft infusion with addback of BPX-501 T cells. AP1903: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment.
  • AP1903

Eligibility Criteria

        Inclusion Criteria:

          1. Age > 1 month and < 26 years

          2. Life expectancy > 10 weeks

          3. Subjects deemed eligible for allogeneic stem cell transplantation.

          4. Subjects with life-threatening hematological malignancies (high-risk ALL in 1st CR,
             ALL in 2nd or subsequent CR, AML in 1st CR, AML in 2nd or subsequent CR,
             myelodysplastic syndromes, non-Hodgkin lymphomas in 2nd or subsequent CR, other
             hematologic malignancies eligible for stem cell transplantation per institutional
             standard);

          5. Non-malignant disorders amenable to cure by an allograft:

               1. primary immune deficiencies,

               2. severe aplastic anemia not responding to immune suppressive therapy,

               3. osteopetrosis,

               4. hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan
                  anemia among others)

               5. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal
                  malignant evolution (MDS, AML) Note: Subjects will be eligible if they meet
                  either item 4 OR item 5.

          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

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

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

          9. Lansky/Karnofsky score > 50

         10. Signed written informed consent

        Exclusion Criteria:

          1. 1. Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous
             allograft at the time of inclusion

          2. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous
             allograft at the time of inclusion

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

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

          5. Current active infectious disease (including positive HIV serology or viral RNA)

          6. Serious concurrent uncontrolled medical disorder

          7. Pregnant or breastfeeding subject

          8. For subjects who have received more than 1 x 10E5 alpha/beta T cells/kg with the graft
             infusion the clinical trial site must contact the sponsor for approval to be eligible
             to receive BPX-501 infusion.
      
Maximum Eligible Age:26 Years
Minimum Eligible Age:1 Month
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:non-relapse/transplant related mortality (TRM/NRM)
Time Frame:1 year
Safety Issue:
Description:To maintain the cumulative incidence of non-relapse/transplant related mortality (TRM/NRM) at 1 year in subjects given the MTD defined during the Phase I portion of the study comparable to that of a historical cohort of subjects given the alpha/beta T-cell depleted HSCT without any T-cell add-back (i.e., below 10%)

Secondary Outcome Measures

Measure:Disease-free survival
Time Frame:2 years
Safety Issue:
Description:Disease-free survival rates after transplantation
Measure:Relapse
Time Frame:1 year
Safety Issue:
Description:Cumulative incidence of relapse
Measure:acute GVHD
Time Frame:1 year
Safety Issue:
Description:Cumulative incidence and severity of acute GVHD
Measure:chronic GVHD
Time Frame:2 years
Safety Issue:
Description:Cumulative incidence and severity of chroonic GVHD
Measure:Kinetics of donor cell engraftment
Time Frame:3 times per week after transplant until the neutrophil count reaches 0.5 x 10E9/L. Thereafter, at least 2 times per week until the neutrophil count is > 1.0 x 10E9/L and platelets > 100 x 10E9/L.
Safety Issue:
Description:time to hematopoietic recovery defined as: neutrophils > 0.5 x 10E9/L for 3 consecutive days together with platelet count > 20 x 10E9/L and without platelet support for 7 consecutive days

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bellicum Pharmaceuticals

Trial Keywords

  • ALL
  • AML
  • hematologic neoplasms
  • hematologic malignancies
  • primary immune deficiences
  • allogeneic stem cell transplant

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