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

Phase I/II Study of CaspaCIDe® T Cells From an HLA-Partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Acute Lymphoblastic Leukemia; Anemia, Aplastic; Primary Immune Deficiency Disorder; Cytopenia; Osteopetrosis; Leukemia, Acute Myeloid (AML), Child; Hemoglobinopathy in Children
• Intervention / Treatment: Biological: BPX-501 T cells; Drug: Rimiducid

Detailed Description

This is a Phase 1/2 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 that does not adequately respond to standard of care therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Boston Children's Cancer and Blood Disorders Center
  • New York
    • Bronx, New York, United States, 10467
      • Children's Hospital at Montefiore
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University - Doernbecher Children's Hospital
  • Texas
    • Dallas, Texas, United States, 77390
      • University of Texas Southwestern-Children's Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/ Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 26 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 1 month and < 26 years
2. Life expectancy > 10 weeks
3. Subjects deemed eligible for allogeneic stem cell transplantation.
4. 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);

5. Non-malignant disorders amenable to cure by an allograft:

   1. primary immune deficiencies,
   2. severe aplastic anemia not responding to immune suppressive therapy,
   3. osteopetrosis,
   4. hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan anemia among others)
   5. 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.
6. 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
7. A minimum genotypic identical match of 5/ 10 is required.
8. 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.
9. Lansky/Karnofsky score > 50
10. Signed written informed consent

Exclusion Criteria:

1. Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion
2. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion
3. Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 mL / min)
4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)
5. Current active infectious disease (including positive HIV serology or viral RNA)
6. Serious concurrent uncontrolled medical disorder
7. Pregnant or breastfeeding subject
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BPX-501 T cells and Rimiducid; 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; T cells transduced with CaspaCIDe® safety switch; Other Names: rivogenlecleucel; Drug: Rimiducid; administered to inactivate BPX-501 cells in the event of GVHD; Other Names: AP1903

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival rates after transplantation	Month 24
Relapse	Cumulative incidence of relapse	Month 12
Engraftment	Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure	Month 24
GvHD	Cumulative incidence and severity of acute and chronic GvHD	Month 24
Rimiducid Efficacy	Time to resolution of acute or chronic GvHD after administration of rimiducid	Month 24
Infection	Rate of infectious complications	Month 24
Hospitalizations	Duration of hospitalization and rehospitalization	Month 24

Collaborators and Investigators

• Sponsor: Bellicum Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2014
• Primary Completion (ACTUAL): May 11, 2021
• Study Completion (ANTICIPATED): May 1, 2034

Study Registration Dates

• First Submitted: September 29, 2017
• First Submitted That Met QC Criteria: October 3, 2017
• First Posted (ACTUAL): October 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 10, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: AML; ALL; hematologic malignancies; hematologic neoplasms; allogeneic stem cell transplant; primary immune deficiences
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Anemia; Bone Diseases; Leukemia, Lymphoid; Bone Marrow Failure Disorders; Lymphoma; Bone Diseases, Developmental; Osteochondrodysplasias; Leukemia, Myeloid; Osteosclerosis; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Anemia, Aplastic; Hemoglobinopathies; Osteopetrosis
• Other Study ID Numbers: BP-U-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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