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

NCT ID: NCT02477878

Last Updated: 2022-07-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2033-01-31

Brief Summary

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.

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.

Conditions

Leukemia; Myelodysplastic Syndromes; Lymphoma; Multiple Myeloma; Hematologic Neoplasms

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

BPX-501

Intervention Type: BIOLOGICAL

Biological: T cells transduced with CaspaCIDe suicide gene

Rimiducid

Intervention Type: DRUG

Rimiducid administered to treat GVHD

Interventions

BPX-501

Biological: T cells transduced with CaspaCIDe suicide gene

Intervention Type: BIOLOGICAL

Rimiducid

Rimiducid administered to treat GVHD

Intervention Type: DRUG

Other Intervention Names

AP1903

Eligibility Criteria

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

• 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.

Locations

BMT Program at Northside Hospital

Atlanta, Georgia, United States

University of Kansas

Westwood, Kansas, United States

Roswell Park

Buffalo, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

UT Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

Other Identifiers

BP-008

Identifier Type: -

Identifier Source: org_study_id