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

• ClinicalTrials.gov Identifier: NCT02477878
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2015
• Last Update Posted: November 19, 2018
• 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

• 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

• 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

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

• Principal Investigator: Madhuri Vusirikala, MD; University of Texas

More 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

• 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:

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