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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndromes; Leukemia; Multiple Myeloma; Lymphomas; Other High-risk Hematological Malignancies
• Intervention / Treatment: Biological: rivogenlecleucel; Drug: Rimiducid

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 Type: Interventional
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of adverse events after study drug (BPX-501 and/or rimiducid) administration as a measure of safety	30 days after last dose of study drug (BPX-501 and/or rimiducid)

Collaborators and Investigators

• Sponsor: Bellicum Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: May 31, 2016
• First Posted (Estimate): June 1, 2016

Study Record Updates

• Last Update Posted (Actual): October 5, 2020
• Last Update Submitted That Met QC Criteria: October 1, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Multiple myeloma; AP1903; Lymphomas; Hematological malignancies; Hematologic diseases; Rimiducid; BPX-501; Leukemias and Myelodysplastic Syndromes
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Precancerous Conditions; Neoplasms; Myelodysplastic Syndromes; Hematologic Neoplasms; Multiple Myeloma; Preleukemia
• Other Study ID Numbers: BP-008-MUD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No