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

NCT ID: NCT02786485

Last Updated: 2020-10-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2018-12-31

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rivogenlecleucel & Rimiducid

All subjects will receive 3 courses of rivogenlecleucel (BPX-501 T cells) infusions at 30 day intervals with 2 escalating dose levels (DL). DL1 on Day 0 and DL2 on Days 30 and 60.

Escalating doses of rimiducid (AP1903) (0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after rivogenlecleucel infusion.

Group Type: EXPERIMENTAL

rivogenlecleucel

Intervention Type: BIOLOGICAL

T cells transduced with iCasp safety switch

Rimiducid

Intervention Type: DRUG

administered to treat GVHD

Interventions

rivogenlecleucel

T cells transduced with iCasp safety switch

Intervention Type: BIOLOGICAL

Rimiducid

administered to treat GVHD

Intervention Type: DRUG

Other Intervention Names

BPX-501; AP1903

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bellicum Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bellicum Pharmaceuticals

Role: STUDY_DIRECTOR

Bellicum Pharmaceuticals, Inc.

Other Identifiers

BP-008-MUD

Identifier Type: -

Identifier Source: org_study_id