Clinical trial NCT03301168: Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Bellicum Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-10-04
Enrollment: 120
Sex: ALL
Minimum age (years): 1
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Adverse Event
timeFrame: Month 24
measure: TRM/NRM
timeFrame: Day 180, Month 12
Secondary outcomes:
measure: Disease-free survival
timeFrame: Month 24
measure: Relapse
timeFrame: Month 12
measure: Engraftment
timeFrame: Month 24
measure: GvHD
timeFrame: Month 24
measure: Rimiducid Efficacy
timeFrame: Month 24
measure: Infection
timeFrame: Month 24
measure: Hospitalizations
timeFrame: Month 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Boston Children's Cancer and Blood Disorders Center
state: Massachusetts
city: Bronx
country: United States
facility: Children's Hospital at Montefiore
state: New York
city: Portland
country: United States
facility: Oregon Health Sciences University - Doernbecher Children's Hospital
state: Oregon
city: Dallas
country: United States
facility: University of Texas Southwestern-Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/ Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Bellicum Pharmaceuticals, Inc.
name: Bellicum Pharmaceuticals
role: STUDY_DIRECTOR
References: