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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02477878
• Other study ID #: BP-008
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 2016
• Est. completion date: January 2033

Study information

• Verified date: July 2022
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: January 2033
• Est. primary completion date: January 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ßHCG 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

Related Conditions & MeSH terms

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

Intervention

Biological:
• BPX-501
Biological: T cells transduced with CaspaCIDe suicide gene

Drug:
• Rimiducid
Rimiducid administered to treat GVHD

Locations

Country	Name	City	State
United States	BMT Program at Northside Hospital	Atlanta	Georgia
United States	Roswell Park	Buffalo	New York
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Kansas	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	GvHD	Assess incidence and severity of acute and chronic GvHD	Month 24
Primary	Rimiducid Activity	Determine the effect of Rimiducid on mitigating GvHD	Month 24
Primary	Rimiducid Efficacy	Assess time to resolution of GvHD after administration of Rimiducid	Month 24
Secondary	Response Rate	Measure overall survival, disease free survival and response rates after BPX-501 infusion	Month 24
Secondary	Translational	Evaluate BPX-501 T cell function	Month 24