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

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Lymphoma

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BPX-501

Rimiducid

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Adult leukemias and myelodysplasia, Adult lymphomas, Adult multiple myeloma, allogeneic stem cell transplant, donor lymphocyte infusion

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects aged >18yrs and < 65yrs
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
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
Signed patient informed consent;
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
Performance status: Karnofsky score > 50%
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:

≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at time of screening;
Active CNS involvement by malignant cells;
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 βHCG test) or breast-feeding;
Subjects of reproductive potential unwilling to use effective forms of birth control or abstinence for a year after transplantation;
Bovine product allergy

Sites / Locations

BMT Program at Northside Hospital
University of Kansas
Roswell Park
Oregon Health & Science University
UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BPX-501 and Rimiducid

Arm Description

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.

Outcomes

Primary Outcome Measures

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

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

GvHD

Assess incidence and severity of acute and chronic GvHD

Rimiducid Activity

Determine the effect of Rimiducid on mitigating GvHD

Rimiducid Efficacy

Assess time to resolution of GvHD after administration of Rimiducid

Secondary Outcome Measures

Response Rate

Measure overall survival, disease free survival and response rates after BPX-501 infusion

Translational

Evaluate BPX-501 T cell function

Full Information

NCT ID

NCT02477878

First Posted

May 18, 2015

Last Updated

July 10, 2022

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02477878

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 2016 (Actual)

Primary Completion Date

January 14, 2020 (Actual)

Study Completion Date

January 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bellicum Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Adult leukemias and myelodysplasia, Adult lymphomas, Adult multiple myeloma, allogeneic stem cell transplant, donor lymphocyte infusion

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BPX-501 and Rimiducid

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

BPX-501

Intervention Description

Biological: T cells transduced with CaspaCIDe suicide gene

Intervention Type

Drug

Intervention Name(s)

Rimiducid

Other Intervention Name(s)

AP1903

Intervention Description

Rimiducid administered to treat GVHD

Primary Outcome Measure Information:

Title

BPX-501 Safety

Description

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

Time Frame

Month 24

Title

Rimiducid Safety

Description

evaluate the safety of the infusion of escalating doses of dimerizer drug rimiducid (AP1903) in subjects who develop acute GvHD after BPX-501 infusion

Time Frame

Month 24

Title

GvHD

Description

Assess incidence and severity of acute and chronic GvHD

Time Frame

Month 24

Title

Rimiducid Activity

Description

Determine the effect of Rimiducid on mitigating GvHD

Time Frame

Month 24

Title

Rimiducid Efficacy

Description

Assess time to resolution of GvHD after administration of Rimiducid

Time Frame

Month 24

Secondary Outcome Measure Information:

Title

Response Rate

Description

Measure overall survival, disease free survival and response rates after BPX-501 infusion

Time Frame

Month 24

Title

Translational

Description

Evaluate BPX-501 T cell function

Time Frame

Month 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects aged >18yrs and < 65yrs Clinical diagnosis of one of the following adult hematological malignancies Leukemia Myelodysplastic Syndromes Lymphomas Multiple myeloma Other high-risk hematologic malignancies eligible for stem cell transplantation per institutional standard Life expectancy >10 weeks Evidence of recurrent disease that presents > 100 days or minimal residual disease (MRD) that presents > 30 days after one of the following: Matched related HSCT Mismatched related HSCT Signed patient informed consent; 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 Performance status: Karnofsky score > 50% Subjects with adequate organ function as measured by: Bone marrow: > 25% donor T-cell chimerism ANC >1 x 10E9/L Cardiac: left ventricular ejection fraction at rest must be >45%. Hepatic: direct bilirubin ≤ 3 x upper limit of normal, or AST/ALT ≤ 5 x upper limit of normal Renal: creatinine ≤ 2x of ULN for age Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin) Exclusion Criteria: ≥ Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at time of screening; Active CNS involvement by malignant cells; 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 βHCG test) or breast-feeding; Subjects of reproductive potential unwilling to use effective forms of birth control or abstinence for a year after transplantation; Bovine product allergy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bellicum Pharmaceuticals

Organizational Affiliation

Bellicum Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

BMT Program at Northside Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

University of Kansas

City

Westwood

State/Province

Kansas

ZIP/Postal Code

66205

Country

United States

Facility Name

Roswell Park

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Oregon Health & Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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