Clinical trial NCT02065869: Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
Official title: Phase I/II Study of CaspaCIDe T Cells (BPX-501; Rivogenlecleucel) From an HLA Partially Matched Family Donor After Negative Selection of TCRαβ+ T Cells in Paediatric Patients Affected by Haematological Disorders
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Lymphoblastic Leukemia
Leukemia, Acute Myeloid (AML), Child
Lymphoma, Non-Hodgkin
Myelodysplastic Syndrome
Primary Immunodeficiency
Anemia, Aplastic
Osteopetrosis
Hemoglobinopathies
Cytopenia
Fanconi Anemia
Diamond Blackfan Anemia
Thalassemia
Anemia, Sickle Cell
Keywords: ALL
AML
hematologic neoplasms
hematologic malignancies
primary immune deficiences
hemoglobinopathy
congenital cytopenia
anemia
Lead sponsor: Bellicum Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-02-19
Enrollment: 187
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
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 I/II 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 who progress or do not respond to standard of care treatment.

Eligibility criteria: Inclusion Criteria:

1. Age \< 18 years and \> 1 month (\< 1 month upon approval by Sponsor)
2. Life expectancy \> 10 weeks
3. Patients deemed clinically eligible for allogeneic stem cell transplantation.
4. Patients may have failed prior allograft
5. Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
6. Non-malignant disorders deemed curable by allogeneic transplantation: (a) primary immune deficiencies, (b) severe aplastic anemia not responding to immune suppressive therapy, (c) osteopetrosis, (d) selected cases of erythroid disorders such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia, (e) congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML).

   Note: Subjects will be eligible if they meet either item 5 OR item 6.
7. 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
8. A minimum genotypic identical match of 5/10 is required.
9. The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1.
10. Lansky/Karnofsky score \> 50
11. Signed informed consent by the patient or the patient's parent or guardian for patients who are minors

Exclusion Criteria:

1. Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
2. Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening
3. Dysfunction of liver (ALT/AST \> 5 times normal value, or bilirubin \> 3 times normal value), or of renal function (creatinine clearance \<30ml/min/1.73m2)
4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction \< 40%)
5. Current clinically active infectious disease (including positive HIV serology or viral RNA)
6. Serious concurrent uncontrolled medical disorder
7. Pregnant or breast feeding female patient
8. Lack of parents'/guardian's informed consent for children who are minors.

Primary outcomes:
measure: Event-free Survival (EFS) at 180 Days After Transplant
timeFrame: 180 days after transplant
Secondary outcomes:
Other outcomes:
Locations:
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
city: London
country: United Kingdom
facility: Royal Free London NHS Foundation Trust
city: London
country: United Kingdom
facility: Institute of Child Health & Great Ormond Street Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Great North Children's Hospital
Study officials:
affiliation: Bellicum Pharmaceuticals, Inc.
name: Bellicum Pharmaceuticals
role: STUDY_DIRECTOR
References: