Leukemia, Lymphomas, Multiple Myeloma, Myelodysplastic Syndromes, Other High-risk Hematological Malignancies
Conditions
Keywords
BPX-501, Rimiducid, AP1903, Hematological malignancies, Hematologic diseases, Leukemias and Myelodysplastic Syndromes, Lymphomas, Multiple myeloma
Brief summary
This is a Phase I, multicenter, open-label, non-randomized study of matched unrelated donor BPX-501 T cell infusion in adult subjects with hematological malignancies presenting with recurrent disease minimal residual disease (MRD) post-allogeneic transplant.
Detailed description
Un-manipulated 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 antigens, as well as against 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). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in safety switch against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve 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 graft-versus-tumor (GvT) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults and children with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.
Interventions
BIOLOGICALrivogenlecleucel
T cells transduced with iCasp safety switch
DRUGRimiducid
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
* Subjects aged ≥ 18 yrs and ≤ 65 yrs; * Clinical diagnosis of one of the following hematological malignancies: * Leukemia * Myelodysplastic Syndromes * Lymphomas * Multiple Myeloma * Other high-risk hematological malignancy eligible for stem cell transplantation per institutional standard; * Recurrent disease that presents ≥100 days after, or minimal residual disease (MRD) that presents ≥ 30 days following a hematopoietic stem cell transplant (HSCT) using a matched unrelated donor located through the National Marrow Donor Program (NMDP); * Life expectancy \>10 weeks; * Signed donor and patient/guardian informed consent; * A 8/8 genotypic identical match as determined by high resolution typing for the following genetic loci: human leukocyte antigen (HLA)-A, HLA-B, HLA-C and HLA-DRB1; * Performance status: Karnofsky score \> 50%; * Subjects with adequate organ function as measured by: * Bone marrow: * \> 25% donor T-cell chimerism post-transplant * Absolute neutrophil count (ANC) \>1 x 109/L * Cardiac: left ventricular ejection fraction (LVEF) at rest ≥ 45% * Pulmonary: forced expiratory volume (FEV) 1, forced vital capacity (FVC), diffusion capacity of lunch for carbon monoxide (DLCO) ≥ 50% predicted (corrected for hemoglobin) * Hepatic: direct bilirubin ≤ 3x upper limit of normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5x ULN * Renal: creatinine ≤ 2x of ULN for age.
Exclusion criteria
* ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of screening; * Active central nervous system (CNS) involvement with malignant cells (≤ 2 months prior to consenting); * 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; * Positive HIV serology or viral RNA; * Pregnancy (positive serum β human chorionic gonadotropin \[HCG\] test) or breast-feeding; * Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation; * Bovine product allergy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 30 days after last dose of study drug (BPX-501 and/or rimiducid) | Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety |
Outcome results
None listed