A Phase 1/2 Dose Escalation Study Evaluating Safety and Feasibility of BPX-501 T Cells After Partially Mismatched, Related, T Cell-Depleted HSCT (Hematopoietic Stem Cell Transplant)
Overview
- Phase
- Phase 1
- Intervention
- BPX-501 dose 1
- Conditions
- Acute Lymphoblastic Leukemia
- Sponsor
- Bellicum Pharmaceuticals
- Enrollment
- 36
- Locations
- 8
- Primary Endpoint
- Rimiducid Safety
- Status
- Active, not recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This study will evaluate patients with blood cell cancers who are going to have an allogeneic (donor) blood stem cell transplant from a partially matched relative. The research study will test whether immune cells, called T cells, which come from the donor relative and are specially grown in the laboratory and then given back to the patient along with the stem cell transplant (T cell addback), can help the immune system recover faster after the transplant. As a safety measure, these T cells have been "programmed" with a "self-destruct switch" so that if, after they have been given to the patient, the T cells start to react against the tissues (called "graft versus host" disease, GVHD), the T cells can be destroyed.
Detailed Description
This is a Phase1/2 dose escalation study evaluating the safety and feasibility of BPX-501 infused after partially mismatched, related (haploidentical), T cell-depleted HSCT. The purpose of this clinical trial is to determine whether BPX-501 infusion can facilitate engraftment, enhance immune reconstitution and potentially improve the graft versus leukemia (GVL) effect, with the potential for reducing the severity and duration of severe acute graft versus host disease (GvHD). The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug (Rimiducid) in those subjects who present with GvHD that does not adequately respond to standard of care therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent
- •Age ≥ 18 years and ≤ 65 years
- •Deemed eligible for allogeneic stem cell transplantation
- •Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
- •HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci
- •A minimum genotypic identical match of 4/8 is required.
- •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, and HLA-DRB1
- •Subjects with adequate organ functions as measured by:
- •Cardiac: Left ventricular ejection fraction at rest must be ≥ 45%
- •Hepatic: Bilirubin ≤ 2.5 mg/dL and ALT, AST and Alkaline Phosphatase \< 5 x ULN
Exclusion Criteria
- •HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate.
- •Autologous hematopoietic stem cell transplant \< 3 months prior to enrollment.
- •Pregnancy or breast-feeding.
- •Evidence of HIV infection or known HIV positive serology.
- •Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). The treating physician will make final determination.
- •Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.
- •Prior allogeneic hematopoietic stem cell transplant.
- •Subjects with a history of primary idiopathic myelofibrosis.
- •Bovine product allergy.
Arms & Interventions
SCT, BPX-501 dose 1, Rimiducid if needed
2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: BPX-501 dose 1
SCT, BPX-501 dose 1, Rimiducid if needed
2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: Rimiducid
SCT, BPX-501 dose 1, Rimiducid if needed
2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: SCT
SCT, BPX-501 dose 2, Rimiducid if needed
5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: Rimiducid
SCT, BPX-501 dose 2, Rimiducid if needed
5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: BPX-501 dose 2
SCT, BPX-501 dose 2, Rimiducid if needed
5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: SCT
SCT, BPX-501 dose 3, Rimiducid if needed
1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: Rimiducid
SCT, BPX-501 dose 3, Rimiducid if needed
1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: BPX-501 dose 3
SCT, BPX-501 dose 3, Rimiducid if needed
1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: SCT
SCT, BPX-501 dose 4, Rimiducid if needed
3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant . Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: Rimiducid
SCT, BPX-501 dose 4, Rimiducid if needed
3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant . Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: BPX-501 dose 4
SCT, BPX-501 dose 4, Rimiducid if needed
3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant . Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.
Intervention: SCT
Outcomes
Primary Outcomes
Rimiducid Safety
Time Frame: 24 months
To evaluate the safety of the infusion of the rimiducid in subjects who received BPX-501 and have developed visceral or steroid refractory graft-versus-host-disease
MTD
Time Frame: 24 months
To determine the maximum dose of BPX-501 (up to 3x106 cells/kg) that results in an adjusted cumulative incidence by Day 100 of no more than 45% Grade II - IV aGVHD and / or no more than 17% Grade III -IV aGVHD.
Immune Reconstitution
Time Frame: 24 months
To assess immune reconstitution for each dose cohort
BPX-501 Safety
Time Frame: 24 months
To evaluate the safety of infusion of each of 4 dose cohorts of BPX-501 (2x105, 5x105, 1x106 and 3x106 cells/kg) after transplantation of partially mismatched T cell depleted hematopoietic stem cell transplant (HSCT)
Secondary Outcomes
- Efficacy- NRM(100, 180 days and 1 year)
- Efficacy- DFS(24 months)
- Efficacy- TRM(24 months)
- Efficacy- Relapse(24 months)
- Incidence of engraftment(24 months)
- GvHD(24 months)
- GvHD post Rimiducid Administration(24 months)
- BPX-501 Safety Profile(24 months)
- Pharmacokinetics of Rimiducid(24 months)