We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety Study of Gene Modified Donor T-Cells in Adults With Advanced Hematologic Malignancies

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.
ClinicalTrials.gov Identifier: NCT02487459
Recruitment Status : Not yet recruiting
First Posted : July 1, 2015
Last Update Posted : January 15, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
This is an open-label, non-randomized study to evaluate the safety of two planned infusions of BPX-501 T cells after partially mismatched, related (haploidentical) HSCT in adults with hematologic malignancies.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Biological: BPX-501 Drug: AP1903 Phase 1

Detailed Description:

The objective is to evaluate the safety of two planned infusions of BPX-501 after partially mismatched, related HSCT with post-transplant cyclophosphamide and to evaluate the safety and efficacy of the treatment of dimerizer drug, rimiducid (AP1903), to subjects who received BPX-501 and have uncontrolled GvHD. Assuming no toxicity, enrollment will proceed sequentially for the initial 9 patients (following the 3+3 design), who will be followed for 100 days, prior to enrolling the subsequent 31 patients. Toxicity may increase the number of initial group of patients). As multiple dose levels may be administered among the first 9 (or more) patients, toxicity will be assessed on the cohort with the maximum tolerated dose (MTD).

Stopping Rules (for the Phase II portion of the study):

  • >20% of patients experience Grade III or IV acute GVHD attributable to BPX-501 T cells and non-responsive to AP1903 infusions.
  • Grade IV reactions related to infusion of BPX-501 or AP1903.
  • Death related to BPX-501 or AP1903 infusions.

The Medical Monitoring committee will review the data with the investigators and determine whether to proceed and or implement any changes to the protocol

BPX-501 contains genetically modified donor T cells that have an inducible safety switch iCasp9 suicide gene. In the event of acute GvHD, administration of rimiducid dimerizes and activates caspase 9; this activates downstream caspases, obligating cellular apoptosis within 24 hours.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Safety Study of Planned BPX-501 T Cell Infusion After Partially Mismatched, Related, HSCT in Adults With Advanced Hematologic Malignances at High Risk for Relapse
Anticipated Study Start Date : February 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : December 2021


Arms and Interventions

Arm Intervention/treatment
Experimental: BPX-501 and AP1903

Three cohorts, 3 patients each, will receive two infusions (at the same dose) of BPX-501.

If needed to treat aGVHD, a single dose of 40 mg of AP1903 will be administered IV.

Biological: BPX-501
T cells transduced with CaspaCIDe suicide gene
Drug: AP1903
dimerizer drug administered to treat GVHD
Other Name: Rimiducid


Outcome Measures

Primary Outcome Measures :
  1. Adverse events [ Time Frame: 2 years ]
    Number of adverse events after BPX-501 as a measure of safety


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: 48 hours ]
    Number of adverse events after AP1903 as a measure of safety


Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Signed informed consent
  2. Patients with one of the life-threatening hematological malignancies:

    • Acute lymphocytic leukemia (ALL) in CR1 with high-risk features including adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; greater than 1 cycle to achiever remission or with persistent MRD; ALL in second or greater remission with or without MRD. Acute myeloid leukemia (AML) in CR1 with high-risk features defined as: Greater than 1 cycle of induction therapy required to achieve remission; Preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; Presence of FLT3 mutations or internal tandem duplications; FAB M6 or M7 classification; Adverse cytogenetics, -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 [> 3 abnormalities];
    • AML in second or greater remission, primary induction failure and patients with relapsed disease;
    • Advanced chronic myeloid leukemia (CML) who have progressed to blast phase or accelerated phase and are in need of a transplant and do not have an HLA matched donor;
    • MDS with IPSS intermediate-2 or higher or therapy-related MDS.Hodgkin lymphoma or Non-Hodgkin lymphoma (NHL): relapsed disease where remission duration is less than 1 year, relapse after previous autologous transplant, or failure to achieve CR with chemotherapy.
  3. Age ≥ 18 years and ≤ 65 years
  4. Deemed eligible for allogeneic stem cell transplantation
  5. 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
  6. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl loci

    • A minimum genotypic identical haplotype 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
  7. Subjects with adequate organs function as measured by:

    • Cardiac: Left ventricular ejection fraction at rest must be >45%
    • Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin); or O2 saturation > 92% on room air
    • Hepatic: Direct bilirubin ≤ 3 x upper limit of normal (ULN), or AST/ALT ≤ 5 x ULN
    • Renal: Serum creatinine within normal range for age or creatinine clearance, or with a recommended GFR ≥ 50 mL/min/1.73m2
  8. Performance status: Karnofsky ≥ 80%

Exclusion Criteria:

Subjects meeting the following criteria are NOT eligible for the study:

  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. Prior allogeneic transplantation;
  4. Active CNS involvement by malignant cells (less than 2 months from the conditioning);
  5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings); the PI is the final arbiter of this criterion;
  6. Positive HIV serology or viral RNA (≥ Grade III per CTCAE criteria);
  7. Pregnancy (positive serum or urine βHCG test) or breast-feeding;
  8. Fertile men or women unwilling to use effective forms of birth control or abstinence for a year after transplantation;
  9. Bovine product allergy.
  10. Severe obesity (patient's weight is >/= 1.5x the donor weight).
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT02487459


Contacts
Contact: Stefan O Ciurea, MD 713-745-0146 sciurea@mdanderson.org

Locations
United States, Texas
MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bellicum Pharmaceuticals
Investigators
Principal Investigator: Stefan O Ciurea, MD Associate Professor, Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center
More Information

Responsible Party: Bellicum Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02487459     History of Changes
Other Study ID Numbers: BP-005
First Posted: July 1, 2015    Key Record Dates
Last Update Posted: January 15, 2018
Last Verified: December 2017
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:
acute lymphoblastic leukemia
acute myeloid leukemia
chronic myeloid leukemia
myelodysplastic syndrome
non-hodgkin lymphoma
hodgkin lymphoma

Additional relevant MeSH terms:
Neoplasms