Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Bellicum Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01744223
First received: December 5, 2012
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

This study will evaluate patients with blood cell cancers who are going to have an allogeneic (donor) blood stem cell transplant from a partially matched relative. The research study will test whether immune cells, called T cells, which come from the donor relative and are specially grown in the laboratory and then given back to the patient along with the stem cell transplant (T cell addback), can help the immune system recover faster after the transplant. As a safety measure, these T cells have been "programmed" with a "self-destruct switch" so that if, after they have been given to the patient, the T cells start to react against the tissues (called "graft versus host" disease, GVHD), the T cells can be destroyed.


Condition Intervention Phase
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Lymphoma
Biological: BPX-501 and AP1903
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Dose Escalation Study Evaluating Safety and Feasibility of BPX-501 T Cells After Partially Mismatched, Related, T Cell-Depleted HSCT (Hematopoietic Stem Cell Transplant)

Resource links provided by NLM:


Further study details as provided by Bellicum Pharmaceuticals:

Primary Outcome Measures:
  • BPX-501 dose that produces no more than 45% Grade II-IV aGVHD and no more than 17% Grade III-IV aGvHD [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    To determine the maximum dose of BPX-501 cells (up to 5 x 10E6 cells/kg) which results in an adjusted cumulative incidence by day 100 of no more than 45% Grade II-IV aGVHD and nor more than 17% Grade III-IV aGvHD. Adjusted cumulative incidence is the total aGvHD cumulative incidence minus the AP1903 GvHD response.


Secondary Outcome Measures:
  • Overall and disease free survival [ Time Frame: 180 days and 1 year ] [ Designated as safety issue: No ]
  • GvHD response to AP1903 [ Time Frame: 100 days, 180 days and 1 year ] [ Designated as safety issue: Yes ]
    The response rates of severe acute GvHD (grades III and IV) in patients receiving AP1903 treatment will be determined at days 100, 180 and 1 year and analyzed by the number of AP1903 infusions and time to resolution of GvHD after last AP1903 infusion


Estimated Enrollment: 36
Study Start Date: March 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BPX-501 and AP1903
BPX-501 and AP1903
Biological: BPX-501 and AP1903

Patients will receive BPX-501 Donor T cells genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene after the stem cell graft infusion is complete, but not more than 72 hours after completion of the stem cell allograft infusion.

AP1903: Dimerizer drug administered (per intravenous infusion ) in those subjects who present with severe GvHD (Grades III and IV) as well as those subjects with Grade I and II who progress or do not respond to corticosteroid therapy within 4 days.


Detailed Description:

This is a Phase1/2 dose escalation study evaluating the safety and feasibility of BPX-501 infused after partially mismatched, related (haploidentical), T cell-depleted HSCT. The purpose of this clinical trial is to determine whether BPX-501 infusion can facilitate engraftment, enhance immune reconstitution and potentially improve the graft versus leukemia (GVL) effect, with the potential for reducing the severity and duration of severe acute graft versus host disease (GvHD). The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903) in those subjects who present with severe GvHD (Grades III and IV) as well as those subjects with Grade I and II who progress or do not respond to corticosteroid therapy within 4 days.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Lack of suitable conventional donor (i.e. 7/8 or 8/8 related or 7/8 or 8/8 unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
  • HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci. A minimum match of 5/10 is required. The donor and recipient must be identical, 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.
  • Subjects with adequate physical function as measured by:a)Cardiac: Left ventricular ejection fraction at rest must be >35%, or shortening fraction > 25%. b)Hepatic: Bilirubin < 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase < 5 x ULN. c)Renal: Serum creatinine within normal range for age, or creatinine clearance or GFR > 40 mL/min/1.73m2. d)Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin); or 02 saturation > 92% on room air.
  • Clinical Diagnosis of one of the following: Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Lymphoma
  • Subjects must have received cytotoxic chemotherapy within 3 months of consent date (measured from the start date of chemotherapy).
  • Performance status: Karnofsky/Lansky score > 60%.

Exclusion Criteria:

  • HLA-matched, related or 7-or 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) unrelated donor able to donate.
  • Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
  • Pregnancy or breast-feeding.
  • Evidence of HIV infection or known HIV positive serology.
  • Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
  • Non-hematologic malignancy within prior three (3) years.
  • Prior allogeneic hematopoietic stem cell transplant.
  • Subjects with a history of primary idiopathic myelofibrosis.
  • Bovine product allergy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01744223

Locations
United States, New York
Roswell Park Not yet recruiting
Buffalo, New York, United States, 14263
Contact: Heather Werner, BBA, CCRP    716-845-1761    heather.werner@roswellpark.org   
Principal Investigator: George Chen, M.D.         
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Allison Feldman    646-888-1018    feldmana@mskcc.org   
Principal Investigator: Miguel-Angel Perales, M.D.         
United States, Ohio
University Hospitals of Cleveland Recruiting
Cleveland, Ohio, United States, 44106
Contact: Marquita Harden    216-844-8051    Marquita.harden@UHhospitals.org   
Principal Investigator: Hillard Lazarus, M.D.         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Chelsea Kline, BA, CCRP    503-418-0128    kline@ohsu.edu   
Principal Investigator: Richard T. Maziarz, M.D.         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Kim Smith, ATC, CCRP    214-648-6551      
Principal Investigator: Madhuri Vusirikala, M.D.         
Sponsors and Collaborators
Bellicum Pharmaceuticals
Investigators
Principal Investigator: Hillard Lazarus, M.D. University Hospital Case Medical Center
  More Information

No publications provided

Responsible Party: Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01744223     History of Changes
Other Study ID Numbers: BP-HM-001
Study First Received: December 5, 2012
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bellicum Pharmaceuticals:
iCaspase9
iCasp9
Inducible Caspase
AP1903
Dimerizer drug
T depleted
Suicide gene
CD-34 selection
haplotransplantation
Graft versus host disease
Allogenic transplantation

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 29, 2014