Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant

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

A Phase I study of BPX-501 T cell infusion in adults with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant. The treatment consists of increasing doses of BPX-501 T cell infusions to achieve a clinical response. Rimiducid will be investigated for the treatment of aGvHD after BPX-501 T cell infusion to determine a dose that can mitigate GvHD and preserve the graft versus leukemia effect.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma; Myelodysplastic Syndromes; Leukemia; Hematologic Neoplasms; Multiple Myeloma
• Intervention / Treatment: Biological: BPX-501; Drug: Rimiducid

Detailed Description

Unmanipulated 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 and 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). BPX-501 contains genetically modified donor T cells that have an inducible safety switch iCasp9 suicide gene. Evidence has emerged that escalating DLI has achieved 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 GvL (graft-versus-leukemia) activity and improve the safety of DLI treatment.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Expanded Access

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

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • BMT Program at Northside Hospital
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • UT southwestern Medical Center

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:

1. Subjects aged >18yrs and < 65yrs

2. Clinical diagnosis of one of the following adult hematological malignancies

   1. Leukemia
   2. Myelodysplastic Syndromes
   3. Lymphomas
   4. Multiple myeloma
   5. Other high-risk hematologic malignancies eligible for stem cell transplantation per institutional standard Life expectancy >10 weeks

3. Evidence of recurrent disease that presents > 100 days or minimal residual disease (MRD) that presents > 30 days after one of the following:

   1. Matched related HSCT
   2. Mismatched related HSCT
4. Signed patient informed consent;
5. A minimum genotypic identical match of 4/8 is required, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA- DRB1
6. Performance status: Karnofsky score > 50%

7. Subjects with adequate organ function as measured by:

   1. Bone marrow:

      • > 25% donor T-cell chimerism
      • ANC >1 x 10E9/L
   2. Cardiac: left ventricular ejection fraction at rest must be >45%.
   3. Hepatic: direct bilirubin ≤ 3 x upper limit of normal, or AST/ALT ≤ 5 x upper limit of normal
   4. Renal: creatinine ≤ 2x of ULN for age
   5. Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin)

Exclusion Criteria:

1. ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at time of screening;
2. Active CNS involvement by malignant cells;
3. 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;
4. Positive HIV serology or viral RNA
5. Pregnancy (positive serum βHCG test) or breast-feeding;
6. Subjects of reproductive potential unwilling to use effective forms of birth control or abstinence for a year after transplantation;
7. 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: BPX-501 and Rimiducid; All subjects will receive 3 cycles of BPX-501 T cell infusions at escalating dose levels (DL). DL1 on Day 0, DL2 on Days 30 and 60. The first dose of BPX-501 T cells will occur ≥30 days after hematopoietic stem cell transplant (HSCT). Two doses of Rimiducid ( 0.1 mg/kg and 0.4 mg/kg) will be investigated for the treatment of aGvHD after BPX-501 T cell infusion.

Biological: BPX-501; Biological: T cells transduced with CaspaCIDe suicide gene; Drug: Rimiducid; Rimiducid administered to treat GVHD; Other Names: AP1903

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BPX-501 Safety	To evaluate the safety of 2 stratified dose levels of BPX-501 T cell infusions based on patient-donor match in adult subjects with hematological malignancies	Month 24
Rimiducid Safety	evaluate the safety of the infusion of escalating doses of dimerizer drug rimiducid (AP1903) in subjects who develop acute GvHD after BPX-501 infusion	Month 24
GvHD	Assess incidence and severity of acute and chronic GvHD	Month 24
Rimiducid Activity	Determine the effect of Rimiducid on mitigating GvHD	Month 24
Rimiducid Efficacy	Assess time to resolution of GvHD after administration of Rimiducid	Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Measure overall survival, disease free survival and response rates after BPX-501 infusion	Month 24
Translational	Evaluate BPX-501 T cell function	Month 24

Collaborators and Investigators

• Sponsor: Bellicum Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): January 14, 2020
• Study Completion (Anticipated): January 1, 2033

Study Registration Dates

• First Submitted: May 18, 2015
• First Submitted That Met QC Criteria: June 18, 2015
• First Posted (Estimate): June 23, 2015

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 10, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: donor lymphocyte infusion; allogeneic stem cell transplant; Adult leukemias and myelodysplasia; Adult lymphomas; Adult multiple myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Hematologic Neoplasms; Multiple Myeloma
• Other Study ID Numbers: BP-008

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