Safety Study of Gene Modified Donor T-cells Following TCR + Alpha Beta Depleted 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: NCT03301168
Recruitment Status : Recruiting
First Posted : October 4, 2017
Last Update Posted : December 11, 2017
Information provided by (Responsible Party):
Bellicum Pharmaceuticals

Brief Summary:
This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (Graft versus host disease).

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Leukemia, Acute Myeloid (AML), Child Lymphoma, Non-Hodgkin Myelodysplastic Syndromes Immunologic Deficiency Syndromes Biological: BPX-501 T cells and AP1903 Drug: AP1903 Phase 1 Phase 2

Detailed Description:

This is a Phase 2 extension study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration severe acute graft versus host disease (GvHD).

The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Extension Study of CaspaCIDe T Cells (BPX-501) From an HLA-partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders
Actual Study Start Date : April 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: BPX-501 T cells and AP1903

TCR alpha beta depleted graft infusion with addback of BPX-501 T cells.

AP1903: Dimerizer drug administered to subjects who develop Grade III-IV acute GVHD, Grade II gut/liver acute GVDH or Grade I/II skin-only acute GvHD which is non-responsive after 7 days of standard of care treatment

Biological: BPX-501 T cells and AP1903
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: 180 days ]
    Number of participants with serious and non-serious adverse events

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age < 18 years and > 1 month (< 1 month upon approval by Sponsor)
  2. Life expectancy > 10 weeks
  3. Patients deemed clinically eligible for allogeneic stem cell transplantation.
  4. Patients may have failed prior allograft
  5. Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
  6. Non-malignant disorders deemed curable by allogeneic transplantation: a. primary immune deficiencies, b. severe aplastic anemia not responding to immune suppressive therapy, c. osteopetrosis d. selected cases of erythroid disorders such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia.

    e. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML).

    Note: Subjects will be eligible if they meet either item 5 OR item 6.

  7. Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically identical relative or 10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
  8. A minimum genotypic identical match of 5/10 is required.
  9. The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1.
  10. Lansky/Karnofsky score > 50
  11. Signed informed consent by the patient or the patient's parent or guardian for patients who are minors

Exclusion Criteria:

  1. Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
  2. Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening
  3. Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance <30ml/min/1.73m2)
  4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)
  5. Current clinically active infectious disease (including positive HIV serology or viral RNA)
  6. Serious concurrent uncontrolled medical disorder
  7. Pregnant or breast feeding female patient
  8. Lack of parents'/guardian's informed consent for children who are minors.

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): NCT03301168

Contact: Neena Kapoor, MD

United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Renna Killen, RN    323-361-2217   
Principal Investigator: Neena Kapoor, MD         
Stanford University; Division of Pediatric Stem Cell Transplant & Regenerative Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Prianka Kumar    650-721-8637      
Principal Investigator: Rajni Agarwal-Hashmi, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Divyesh Kukadiya    202-476-6850   
Principal Investigator: David Jacobsohn, MD, ScM         
United States, Georgia
Children's Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30322
Contact: Ashley Griffin    404-785-0653   
Principal Investigator: Lakshmanan Krishnamurti, MD         
United States, Massachusetts
Dana-Farber Boston Children's Cancer and Blood Disorders Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Colleen Dansereau    617-919-7008   
Principal Investigator: Susanne Baumeister, MD         
United States, New York
Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Ruth Santizo    718-920-6506   
Principal Investigator: Deepa Manwani, MD         
United States, Oregon
Oregon Health Sciences University - Doernbecher Children's Hospital Recruiting
Portland, Oregon, United States, 97239
Contact: Jennifer Williamson    503-494-3639   
Principal Investigator: Eneida Nemecek, MD         
United States, Texas
University of Texas Southwestern-Children's Medical Center Recruiting
Dallas, Texas, United States, 77390
Contact: Gevel Jackson, CCRP    214-456-1430   
Principal Investigator: Victor M Aquino, MD         
Baylor College of Medicine/ Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Marlen Dinu    832-824-4881   
Principal Investigator: Swati Naik, MD         
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Michelle Bouvier    206-667-6993   
Principal Investigator: Lauri M Burroughs, MD         
Sponsors and Collaborators
Bellicum Pharmaceuticals
Principal Investigator: Neena Kapoor, MD Children's Hospital of LA

Responsible Party: Bellicum Pharmaceuticals Identifier: NCT03301168     History of Changes
Other Study ID Numbers: BP-U-004
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Bellicum Pharmaceuticals:
hematologic neoplasms
hematologic malignancies
primary immune deficiences

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Immunologic Deficiency Syndromes
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases