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. Read our disclaimer for details. Identifier: NCT01744223
Recruitment Status : Active, not recruiting
First Posted : December 6, 2012
Last Update Posted : October 15, 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

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

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 : March 2020
Estimated Study Completion Date : December 2020

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

Information from the National Library of Medicine

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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:

  1. Signed informed consent
  2. Age ≥ 18 years and ≤ 65 years
  3. Deemed eligible for allogeneic stem cell transplantation
  4. Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
  5. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci

    • A minimum genotypic identical match of 4/8 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
  6. Subjects with adequate organ functions as measured by:

    1. Cardiac: Left ventricular ejection fraction at rest must be ≥ 45%
    2. Hepatic: Bilirubin ≤ 2.5 mg/dL and ALT, AST and Alkaline Phosphatase < 5 x ULN
    3. Renal: Serum creatinine within normal range for age or creatinine clearance, or with a recommended GFR ≥ 50 mL/min/1.73m2
    4. Pulmonary: FEV 1, FVC and DLCO (diffusion capacity) ≥ 50% predicted (corrected for hemoglobin); or O2 saturation > 92% on room air
  7. Clinical diagnosis of one of the following:

    a. Acute Leukemia (includes T lymphoblastic lymphoma) in 2nd or subsequent complete remission (CR) i. Acute Lymphoblastic Leukemia (ALL) in 2nd or subsequent CR. ALL shall be morphologic remission at the time of transplant. Morphologic remission is defined that subjects with normal neutrophil and platelet counts, less than 5% blast cells in a bone marrow (BM) smear and no extramedullary disease ii. Acute Myeloid Leukemia (AML) in 2nd or subsequent CR with or without persistent minimal residual disease b. High-risk ALL in 1st CR (including features such as those in i-iii) i. Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements ii. Subjects over 30 years of age, or iii. Time to complete remission was greater than 4 weeks. c. High-risk AML in 1st CR (including features such as those listed in i-vii) i. Greater than 1 cycle of induction therapy required to achieve remission ii. Preceding myelodysplastic syndrome (MDS) iii. Presence of FLT3 abnormalities iv. FAB M6 or M7 leukemia v. Adverse cytogenetics for overall survival such as those associated with MDS vi. Complex karyotype (>3 abnormalities), or vii. Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)], t(l1;19)(q23;p13.1) d. High risk Myelodysplastic Syndrome e. Non-Hodgkin's Lymphoma relapsed after autologous transplantation f. Non-Hodgkin's Lymphoma with insufficient autologous hematopoietic stem cells to undergo autologous transplantation g. CML i. in first chronic phase that has not attained at least a complete cytogenetic remission after exposure to at least 3 tyrosine kinase inhibitors ii. in accelerated phase that has not attained at least a complete cytogenetic remission iii. in second chronic phase

  8. Performance status: Karnofsky score ≥60%.
  9. Patient with hematologic malignancy not responding to /or not eligible for conventional therapy and are approved by Sponsor

Exclusion Criteria:

  1. HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate.
  2. Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
  3. Pregnancy or breast-feeding.
  4. Evidence of HIV infection or known HIV positive serology.
  5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings). The treating physician will make final determination.
  6. Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma.
  7. Prior allogeneic hematopoietic stem cell transplant.
  8. Subjects with a history of primary idiopathic myelofibrosis.
  9. 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
Atlanta, Georgia, United States, 30322
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
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
Principal Investigator: Richard Maziarz, M.D. Oregon Health and Science University

Responsible Party: Bellicum Pharmaceuticals Identifier: NCT01744223     History of Changes
Other Study ID Numbers: BP-001
First Posted: December 6, 2012    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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