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

• ClinicalTrials.gov Identifier: NCT02786485
• Recruitment Status: Withdrawn
• First Posted: June 1, 2016
• Last Update Posted: October 5, 2020
• Sponsor: Bellicum Pharmaceuticals
• Information provided by (Responsible Party): Bellicum Pharmaceuticals

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

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 (Clinical Trial)
• 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 2016
• Actual Primary Completion Date: December 2018
• Actual Study Completion Date: December 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 Name: BPX-501; Drug: Rimiducid; administered to treat GVHD; Other Name: AP1903

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: 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

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

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.

Contacts and Locations

Sponsors and Collaborators

Bellicum Pharmaceuticals

Investigators

• Study Director: Bellicum Pharmaceuticals; Bellicum Pharmaceuticals, Inc.

More Information

• Responsible Party: Bellicum Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02786485
• Other Study ID Numbers: BP-008-MUD
• First Posted: June 1, 2016
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bellicum Pharmaceuticals:

BPX-501; Rimiducid; AP1903; Hematological malignancies; Hematologic diseases; Leukemias and Myelodysplastic Syndromes; Lymphomas; Multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms; Preleukemia; Hematologic Neoplasms; Myelodysplastic Syndromes; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Bone Marrow Diseases; Precancerous Conditions; Neoplasms by Site