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

Sponsor

Bellicum Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03301168

Collaborator

(none)

120

Enrollment

Locations

Arm

241

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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

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

Anticipated 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 :

Apr 1, 2014

Actual Primary Completion Date :

May 11, 2021

Anticipated Study Completion Date :

May 1, 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 Names: rivogenlecleucel Drug: Rimiducid administered to inactivate BPX-501 cells in the event of GVHD Other Names: AP1903

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 26 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion
Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
2	Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine	Palo Alto	California	United States	94304
3	Children's National Medical Center	Washington	District of Columbia	United States	20010
4	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
5	Dana-Farber Boston Children's Cancer and Blood Disorders Center	Boston	Massachusetts	United States	02215
6	Children's Hospital at Montefiore	Bronx	New York	United States	10467
7	Oregon Health Sciences University - Doernbecher Children's Hospital	Portland	Oregon	United States	97239
8	University of Texas Southwestern-Children's Medical Center	Dallas	Texas	United States	77390
9	Baylor College of Medicine/ Texas Children's Hospital	Houston	Texas	United States	77030
10	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109