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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01744223
Recruitment Status : Recruiting
First Posted : December 6, 2012
Last Update Posted : March 20, 2018
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

Brief Summary:
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 or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Lymphoma Biological: BPX-501 and AP1903 Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : March 2013
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Disease-free survival [ Time Frame: 180 days and 1 year ]
    Disease-free survival rate after transplantation

  2. GvHD response to AP1903 [ Time Frame: 100 days, 180 days and 1 year ]
    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

  3. Event free survival [ Time Frame: 180 days and 1 year ]
    Event free survival rate after transplantation

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01744223

United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Neera Jagirdar    404-778-3708   
Principal Investigator: Zaid Al-Kadhimi, MD         
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Angela Kader    716-845-4485   
Principal Investigator: George Chen, M.D.         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Chelsea Kline, BA, CCRP    503-418-0128   
Principal Investigator: Richard T. Maziarz, M.D.         
United States, Tennessee
Vanderbilt University Withdrawn
Nashville, Tennessee, United States, 37212
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Ryan Woelfel, CRC    214-648-5130   
Principal Investigator: Madhuri Vusirikala, M.D.         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Michele Bouvier    206-667-6993   
Principal Investigator: Brenda M Sandmaier, MD         
Sponsors and Collaborators
Bellicum Pharmaceuticals
Principal Investigator: Hillard Lazarus, M.D. University Hospitals Cleveland Medical Center

Responsible Party: Bellicum Pharmaceuticals Identifier: NCT01744223     History of Changes
Other Study ID Numbers: BP-HM-001
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: March 20, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

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