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

• ClinicalTrials.gov Identifier: NCT03301168
• Recruitment Status: Active, not recruiting
• First Posted: October 4, 2017
• Last Update Posted: October 5, 2020
• Sponsor: Bellicum Pharmaceuticals
• Information provided by (Responsible Party): Bellicum Pharmaceuticals

Study Description

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; Primary Immune Deficiency Disorder; Osteopetrosis; Cytopenia; Hemoglobinopathy in Children; Anemia, Aplastic	Biological: BPX-501 T cells; Drug: Rimiducid	Phase 1; Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 2014
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2034

Arms and Interventions

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 Name: rivogenlecleucel; Drug: Rimiducid; administered to inactivate BPX-501 cells in the event of GVHD; Other Name: AP1903

Outcome Measures

Primary Outcome Measures :

1. Adverse Event [ Time Frame: Month 24 ]
   Demonstrate safety of BPX-501 MTD
2. TRM/NRM [ Time Frame: Day 180, Month 12 ]
   Assess the cumulative incidence of non-relapse/transplant related mortality

Secondary Outcome Measures :

1. Disease-free survival [ Time Frame: Month 24 ]
   Disease-free survival rates after transplantation
2. Relapse [ Time Frame: Month 12 ]
   Cumulative incidence of relapse
3. Engraftment [ Time Frame: Month 24 ]
   Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure
4. GvHD [ Time Frame: Month 24 ]
   Cumulative incidence and severity of acute and chronic GvHD
5. Rimiducid Efficacy [ Time Frame: Month 24 ]
   Time to resolution of acute or chronic GvHD after administration of rimiducid
6. Infection [ Time Frame: Month 24 ]
   Rate of infectious complications
7. Hospitalizations [ Time Frame: Month 24 ]
   Duration of hospitalization and rehospitalization

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 26 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

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

Palo Alto, California, United States, 94304

United States, District of Columbia

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Georgia

Children's Healthcare of Atlanta

Atlanta, Georgia, United States, 30322

United States, Massachusetts

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

Boston, Massachusetts, United States, 02215

United States, New York

Children's Hospital at Montefiore

Bronx, New York, United States, 10467

United States, Oregon

Oregon Health Sciences University - Doernbecher Children's Hospital

Portland, Oregon, United States, 97239

United States, Texas

University of Texas Southwestern-Children's Medical Center

Dallas, Texas, United States, 77390

Baylor College of Medicine/ Texas Children's Hospital

Houston, Texas, United States, 77030

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Bellicum Pharmaceuticals

Investigators

• Study Director: Bellicum Pharmaceuticals; Bellicum Pharmaceuticals, Inc.

More Information

• Responsible Party: Bellicum Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03301168
• Other Study ID Numbers: BP-U-004
• First Posted: October 4, 2017
• Last Update Posted: October 5, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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:

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

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Myeloid, Acute; Osteopetrosis; Myelodysplastic Syndromes; Hemoglobinopathies; Anemia, Aplastic; Immunologic Deficiency Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Genetic Diseases, Inborn; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Anemia; Leukemia, Myeloid