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

Sponsor

Bellicum Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02477878

Collaborator

(none)

Enrollment

Locations

Arm

198

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes Lymphoma Multiple Myeloma Hematologic Neoplasms	Biological: BPX-501 Drug: Rimiducid	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 1, 2016

Actual Primary Completion Date :

Jan 14, 2020

Anticipated Study Completion Date :

Jan 1, 2033

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

BPX-501 Safety [Month 24]
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 [Month 24]
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 [Month 24]
Assess incidence and severity of acute and chronic GvHD
Rimiducid Activity [Month 24]
Determine the effect of Rimiducid on mitigating GvHD
Rimiducid Efficacy [Month 24]
Assess time to resolution of GvHD after administration of Rimiducid

Secondary Outcome Measures

Response Rate [Month 24]
Measure overall survival, disease free survival and response rates after BPX-501 infusion
Translational [Month 24]
Evaluate BPX-501 T cell function

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BMT Program at Northside Hospital	Atlanta	Georgia	United States	30342
2	University of Kansas	Westwood	Kansas	United States	66205
3	Roswell Park	Buffalo	New York	United States	14263
4	Oregon Health & Science University	Portland	Oregon	United States	97239
5	UT Southwestern Medical Center	Dallas	Texas	United States	75390