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

Sponsor

Bellicum Pharmaceuticals (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02786485

Collaborator

(none)

Enrollment

Arm

Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes Lymphomas Multiple Myeloma Other High-risk Hematological Malignancies	Biological: rivogenlecleucel Drug: Rimiducid	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of Matched Unrelated Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant

Actual Study Start Date :

May 1, 2016

Actual Primary Completion Date :

Dec 1, 2018

Actual Study Completion Date :

Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: rivogenlecleucel T cells transduced with iCasp safety switch Other Names: BPX-501 Drug: Rimiducid administered to treat GVHD Other Names: AP1903

Arm

Intervention/Treatment

Experimental: 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.

Biological: rivogenlecleucel

T cells transduced with iCasp safety switch

Other Names:

BPX-501

Drug: Rimiducid

administered to treat GVHD

Other Names:

AP1903

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.