Leukemia, Myelodysplastic Syndromes, Lymphoma, Multiple Myeloma, Hematologic Neoplasms
Conditions
Keywords
Adult leukemias and myelodysplasia, Adult lymphomas, Adult multiple myeloma, allogeneic stem cell transplant, donor lymphocyte infusion
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. Rimiducid 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.
Interventions
BIOLOGICALBPX-501
Biological: T cells transduced with CaspaCIDe suicide gene
DRUGRimiducid
Rimiducid administered to treat GVHD
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rimiducid Safety | Month 24 | evaluate the safety of the infusion of escalating doses of dimerizer drug rimiducid (AP1903) in subjects who develop acute GvHD after BPX-501 infusion |
| Rimiducid Activity | Month 24 | Determine the effect of Rimiducid on mitigating GvHD |
| Rimiducid Efficacy | Month 24 | Assess time to resolution of GvHD after administration of Rimiducid |
| BPX-501 Safety | Month 24 | 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 |
| GvHD | Month 24 | Assess incidence and severity of acute and chronic GvHD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Translational | Month 24 | Evaluate BPX-501 T cell function |
| Response Rate | Month 24 | Measure overall survival, disease free survival and response rates after BPX-501 infusion |
Countries
United States
Outcome results
None listed