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

Myelodysplastic Syndromes Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03301168
• Other study ID #: BP-U-004
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 2014
• Est. completion date: May 2034

Study information

• Verified date: May 2022
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: May 2034
• Est. primary completion date: May 11, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 26 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Anemia, Aplastic
• Cytopenia
• Hemoglobinopathies
• Hemoglobinopathy in Children
• Immunologic Deficiency Syndromes
• Leukemia
• Leukemia, Acute Myeloid (AML), Child
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndromes
• Osteopetrosis
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Primary Immune Deficiency Disorder
• Primary Immunodeficiency Diseases

Intervention

Biological:
• BPX-501 T cells
T cells transduced with CaspaCIDe® safety switch

Drug:
• Rimiducid
administered to inactivate BPX-501 cells in the event of GVHD

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Dana-Farber Boston Children's Cancer and Blood Disorders Center	Boston	Massachusetts
United States	Children's Hospital at Montefiore	Bronx	New York
United States	University of Texas Southwestern-Children's Medical Center	Dallas	Texas
United States	Baylor College of Medicine/ Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine	Palo Alto	California
United States	Oregon Health Sciences University - Doernbecher Children's Hospital	Portland	Oregon
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Event	Demonstrate safety of BPX-501 MTD	Month 24
Primary	TRM/NRM	Assess the cumulative incidence of non-relapse/transplant related mortality	Day 180, Month 12
Secondary	Disease-free survival	Disease-free survival rates after transplantation	Month 24
Secondary	Relapse	Cumulative incidence of relapse	Month 12
Secondary	Engraftment	Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure	Month 24
Secondary	GvHD	Cumulative incidence and severity of acute and chronic GvHD	Month 24
Secondary	Rimiducid Efficacy	Time to resolution of acute or chronic GvHD after administration of rimiducid	Month 24
Secondary	Infection	Rate of infectious complications	Month 24
Secondary	Hospitalizations	Duration of hospitalization and rehospitalization	Month 24