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

• Sponsor: Bellicum Pharmaceuticals
• Information provided by (Responsible Party): Bellicum Pharmaceuticals

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. AP1903 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: AP1903	Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
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 :	July 2016
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: BPX-501 and AP1903; 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 AP1903 ( 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: AP1903; AP1903 administered to treat GVHD; Other Name: Rimiducid

Outcome Measures

Primary Outcome Measures :

1. Adverse events [ Time Frame: 1 year ]
   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
2. Adverse events [ Time Frame: 36 hours ]
   evaluate the safety of the infusion of escalating doses of dimerizer drug rimiducid (AP1903) in subjects who develop acute GvHD after BPX-501 infusion

Secondary Outcome Measures :

1. Response Rate [ Time Frame: 2 years ]
   Measure overall survival and disease free survival 2 years after BPX-501 infusion

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Locations

Layout table for location information

United States, Georgia
BMT Program at Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Kansas
University of Kansas
Westwood, Kansas, United States, 66205
United States, New York
Roswell Park
Buffalo, New York, United States, 14263
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Bellicum Pharmaceuticals

Investigators

Layout table for investigator information

Principal Investigator:	Madhuri Vusirikala, MD	University of Texas

More Information

Layout table for additonal information

Responsible Party:	Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02477878 History of Changes
Other Study ID Numbers:	BP-008
First Posted:	June 23, 2015
Last Update Posted:	November 19, 2018
Last Verified:	November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:		Yes

Keywords provided by Bellicum Pharmaceuticals:

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

Additional relevant MeSH terms:

Layout table for MeSH terms

Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Preleukemia; Hematologic Neoplasms; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases	Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Precancerous Conditions; Neoplasms by Site