Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic 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: NCT02477878
Recruitment Status : Recruiting
First Posted : June 23, 2015
Last Update Posted : January 16, 2018
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

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 tumor effect.

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

Detailed Description:
Un-manipulated 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 antigens, as well as against 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). The use of a suicide gene switch which would trigger the initiation of the apoptosis of the alloreactive T cells by the infusion of a drug would represent the potential optimal strategy for restoring early immunity with a built in "safety switch" against GvHD side effects. Evidence has emerged that low-dose DLI followed by dose escalation can achieve 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 GvT (graft-versus-tumor) activity and improve the safety of DLI treatment. Our strategy is to infuse escalating doses of manipulated T cells (from the same donor who provided the original hematopoietic stem cell graft) in adults with recurrent or minimal residual disease (MRD) hematologic malignancies post-allogeneic transplant to accelerate immune reconstitution thus improving graft versus leukemic effect while reducing the severity of GvHD.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Donor BPX-501 T Cell Infusion for Adults With Recurrent or Minimal Residual Disease Hematologic Malignancies Post-Allogeneic Transplant
Study Start Date : July 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

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

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

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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. Clinical diagnosis of one of the following:

    1. leukemia
    2. myelodysplasia
    3. lymphoma
    4. multiple myeloma
    5. Other high-risk hematologic malignancies eligible for stem cell transplantation per institutional standard
  2. Recurrent disease that presents >100 days after, or minimal residual disease (MRD) that presents > 30 days after either:

    1. Matched related HSCT
    2. Mismatched related HSCT
  3. Life expectancy >10 weeks;
  4. Signed donor and patient/guardian 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/Lansky score > 50%.
  7. Subjects with adequate organ function as measured by:

    1. Bone marrow: > 25% donor T-cell chimerism in peripheral blood, obtained after 3 weeks post-transplant; ANC >1 x 10E9/L
    2. Cardiac: left ventricular ejection fraction at rest must be ≥ 45%
    3. Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) ≥ 50% predicted (corrected for hemoglobin)
    4. Hepatic: direct bilirubin ≤ 3 x upper limit of normal, or AST/ALT ≤ 5 x upper limit of normal
    5. Renal: creatinine ≤ 2x of ULN for age

Exclusion Criteria:

  1. ≥ Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
  2. Active CNS involvement by malignant cells (≤ 2 months from the conditioning)
  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 or urine βHCG test) or breast-feeding
  6. Fertile men or women unwilling to use effective forms of birth control or abstinence for one year after transplantation
  7. 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): NCT02477878

United States, Georgia
BMT Program at Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Brandy Baker-Garner, RN    404-255-1930   
Principal Investigator: Scott R Solomon, MD         
United States, Kansas
University of Kansas Recruiting
Westwood, Kansas, United States, 66205
Contact: Renee Sol   
Principal Investigator: Joseph McGuirk, MD         
United States, New York
Roswell Park Recruiting
Buffalo, New York, United States, 14263
Contact: Heather Werner, BBA, CCRP    716-845-1761   
Principal Investigator: George Chen, M.D.         
Weill Cornell Medical College Withdrawn
New York, New York, United States, 10065
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Chelsea Kline    503-418-0128   
Principal Investigator: Richard T Maziarz, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Shireen Williams    615-875-6278   
Principal Investigator: Michael Byrne, MD         
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 Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Michelle Bouvier    206-667-6993   
Principal Investigator: Brenda Sandmaier, MD         
Sponsors and Collaborators
Bellicum Pharmaceuticals
Principal Investigator: Madhuri Vusirikala, MD University of Texas

Responsible Party: Bellicum Pharmaceuticals Identifier: NCT02477878     History of Changes
Other Study ID Numbers: BP-008
First Posted: June 23, 2015    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Bellicum Pharmaceuticals:
Adult leukemias and myelodysplasia
Adult lymphomas
Adult multiple myeloma

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases