Study of Matched Unrelated Donor T Cell Infusion for Hematologic Malignancies After Allo-HSCT

Bellicum Pharmaceuticals

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Conditions

Leukemia Myelodysplastic Syndromes Lymphomas Multiple Myeloma Other High-risk Hematological Malignancies

Interventions

rivogenlecleucelBIOLOGICAL

T cells transduced with iCasp safety switch

RimiducidDRUG

administered to treat GVHD

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Adverse events

Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety

Time frame: 30 days after last dose of study drug (BPX-501 and/or rimiducid)

Data from ClinicalTrials.gov

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