Phase I/II study of CaspaCide T cells in children following aß- depleted mis-matched family donor stem cell transplantatio

Phase 1

• Conditions: Hematological disorders (ALL; AML; Non-Hodgkin lymphoma; Myelodysplastic syndromes; Congenital immune deficiencies; Severe aplastic anemia; Fanconi anemia; Osteopetrosis; Selected cases of hemoglobinopathies); MedDRA version: 20.0Level: HLGTClassification code 10018849Term: Haematological disorders NECSystem Organ Class: 10005329 - Blood and lymphatic system disorders

• Registration Number: EUCTR2014-000584-41-GB
• Lead Sponsor: Bellicum Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-07-15
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

Patient Inclusion Criteria:
1. Males or females
2. Age = 18 years and = 1 month (<1 month upon approval by Sponsor)
3. Life expectancy > 10 weeks
4. Patients deemed clinically eligible for allogeneic stem cell transplantation.
5. Patients may have failed a prior allograft.
6. Patients with life-threatening acute leukemia (high-risk Acute Lymphoblastic leukemia (ALL) in 1st Complete remission (CR), ALL in 2nd CR, high-risk Acute Myeloid leukemia (AML) in 1st CR, AML in 2nd CR). Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
7. Non-malignant disorders deemed curable by allogenic transplantation:
a. primary immune deficiencies,
b. severe aplastic anemia not responding to immune suppressive therapy,
c. osteopetrosis,
d. selected cases of erythoid disorders, such as ß0 ß0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia,
e. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (Myelodysplastic syndrome (MDS), AML).
Note: subjects will be eligible if they meet either item 6 or 7.
8. Lack of suitable conventional donor (Human Leucocyte Antigene (HLA) identical sibling or HLA phenotypically identical relative or 9-10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
9. A minimum genotypic identical match of 5/10 is required
10. 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.
11. Lansky/Karnofsky score > 50
12. Signed written informed consent by the patient or the patient's parent or guardian for patients who are minors

Donor
1. Eligible donors include 5/10 HLA identical relative, including but not limited to biological parents, siblings, or half-siblings. Matching will be determined by class I and class II DNA typing. The donor of the BPX-501 T cells must be the HSCT donor.
2. Donor age must be > 18 and < 65 years.
3. The donor should be sufficiently healthy not to be at increased risk from the mobilization procedure.
4. Should more than one equally” MHC compatible donor be identified, other selection criteria may include natural killer cell (NK) alloreactivity, NK cell KIR-Haplotype, B-content for B-haplotype donors, size of the NK alloreactive subset, gender, age, CMV status, health status and body weight of donor. The physician treating the subject will make the final decision.
5. Donors must meet the selection criteria as defined by the European Directive 2006/17/CE and according to the FACT-JACIE International Standards and local regulations for donor selection.
6. The donor must have been informed of the investigational nature of the BPX-501 product and have signed an informed consent form that they will undergo a second pheresis procedure.
7. Donor must have adequate peripheral venous access for leukapheresis or must agree to placement of a central venous catheter.
8. The collection of donor T cells to be transduced with the suicide gene will be performed before the mobilization procedure with G-CSF in order to avoid any potential negative influence of this cytokine on function of genetically modified T cells.
9. Signed informed consent

Are the trial subjects under 18? yes
Number of subjects for this age range: 175
F.1.2 Adults (18-6

Exclusion Criteria

Patient
1. Greater than grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion
2. Patient receiving an immunosuppressive treatment for GVHD treatment due o 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 uncontrolled 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

Donor exclusion criteria
1. Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or viral hepatitis exposure (on screening), unless HBs Ab+ and HBV DNA negative.
2. Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy, previous thrombotic events).
3. Pregnancy at the time of normal leukapheresis for the T cells and at the time of the mobilization for the stem cell allograft collection.
4. Breastfeeding at the time of mobilization

Sponsor will be notified of any AEs (infections, etc.) occurring in the donor between the leukapheresis and stem cell apheresis.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified