Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant

NCT03301168 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: BP-U-004
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 10

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).

Conditions

Acute Lymphoblastic Leukemia; Leukemia, Acute Myeloid (AML), Child; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Primary Immune Deficiency Disorder; Osteopetrosis; Cytopenia; Hemoglobinopathy in Children; Anemia, Aplastic

Keywords

ALL; AML; hematologic neoplasms; hematologic malignancies; primary immune deficiences; allogeneic stem cell transplant

Outcome Measures

Primary Outcomes (2)

• Adverse Event

  Demonstrate safety of BPX-501 MTD

  Month 24

• TRM/NRM

  Assess the cumulative incidence of non-relapse/transplant related mortality

  Day 180, Month 12

Secondary Outcomes (7)

• Disease-free survival

  Month 24

• Relapse

  Month 12

• Engraftment

  Month 24

• GvHD

  Month 24

• Rimiducid Efficacy

  Month 24

Study Arms (1)

BPX-501 T cells and Rimiducid

EXPERIMENTAL

TCR alpha beta depleted graft infusion with addback of BPX-501 T cells. Rimiducid: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment.

Biological: BPX-501 T cells; Drug: Rimiducid

Interventions

BPX-501 T cells BIOLOGICAL

T cells transduced with CaspaCIDe® safety switch

Also known as: rivogenlecleucel

BPX-501 T cells and Rimiducid

Rimiducid DRUG

administered to inactivate BPX-501 cells in the event of GVHD

Also known as: AP1903

BPX-501 T cells and Rimiducid

Eligibility Criteria

• Age: 1 Month - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \> 1 month and \< 26 years
• Life expectancy \> 10 weeks
• Subjects deemed eligible for allogeneic stem cell transplantation.
• Subjects with life-threatening hematological malignancies (high-risk ALL in 1st CR, ALL in 2nd or subsequent CR, AML in 1st CR, AML in 2nd or subsequent CR, myelodysplastic syndromes, non-Hodgkin lymphomas in 2nd or subsequent CR, other hematologic malignancies eligible for stem cell transplantation per institutional standard);
• Non-malignant disorders amenable to cure by an allograft:
• primary immune deficiencies,
• severe aplastic anemia not responding to immune suppressive therapy,
• osteopetrosis,
• hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan anemia among others)
• congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML) Note: Subjects will be eligible if they meet either item 4 OR item 5.
• 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
• A minimum genotypic identical 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, HLA- DRB1 and HLA-DQB1.
• Lansky/Karnofsky score \> 50
• Signed written informed consent

You may not qualify if:

• Dysfunction of liver (ALT/AST \> 5 times normal value, or bilirubin \> 3 times normal value), or of renal function (creatinine clearance \< 30 mL / min)
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction \< 40%)
• Current active infectious disease (including positive HIV serology or viral RNA)
• Serious concurrent uncontrolled medical disorder
• Pregnant or breastfeeding subject
• For subjects who have received more than 1 x 10E5 alpha/beta T cells/kg with the graft infusion the clinical trial site must contact the sponsor for approval to be eligible to receive BPX-501 infusion.

Sponsors & Collaborators

• Bellicum Pharmaceuticals: lead

Study Sites (10)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine

Palo Alto, California, 94304, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Dana-Farber Boston Children's Cancer and Blood Disorders Center

Boston, Massachusetts, 02215, United States

Location

Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Oregon Health Sciences University - Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern-Children's Medical Center

Dallas, Texas, 77390, United States

Location

Baylor College of Medicine/ Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Primary Immunodeficiency Diseases; Osteopetrosis; Cytopenia; Anemia, Aplastic; Hematologic Neoplasms

Interventions

AP 1903 reagent

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Lymphoma; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Anemia; Bone Marrow Failure Disorders; Neoplasms by Site

Study Officials

• Bellicum Pharmaceuticals

  Bellicum Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 4, 2017
• Study Start: April 1, 2014
• Primary Completion: May 11, 2021
• Study Completion (Estimated): May 1, 2034
• Last Updated: July 12, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)