Health Condition 1: C910- Acute lymphoblastic leukemia [ALL] Health Condition 2: C851- Unspecified B-cell lymphoma
Conditions
Interventions
Intervention1: HCAR19 for relapsed refractory B ALL: A humanized Second generation anti CD19 CAR construct HCAR 19 with 4 1BB co stimulatory domain has been designed and developed at IIT Bombay. Both
Sponsors
Tata Memorial Hospital Research Administrative Council
Immunoadoptive Cell Therapy Private Limited ImmunoACT
Eligibility
Inclusion criteria
Inclusion criteria: a. Disease Criteria: i. Relapsed or refractory pediatric, adolescent or young adult (3-25 years at screening) with B-cell ALL. ii. Relapse for the purpose of this study is defined as 1. Presence of > 5% blasts at screening, and confirmation by FCM, AND 2. Second or subsequent bone marrow (BM) relapse, OR 3. Any BM relapse after allogeneic SCT 4. First Relapse will be considered if: 1. First Relapse has occurred very early, within 18 months of initial diagnosis 2. Is not in remission after re-induction chemotherapy as defined by FSM MRD 3. First Relapse in High-risk groups such as Ph+ and Ph-like ALL, and other known poor-prognostic cytogenetics/molecular profiles iii. Refractory B-ALL is defined as: 1. Not achieving an initial CR after 2 cycles of a standard chemotherapy regimen (primary refractory). AND 2. Such patients have received 1 or more lines of second line or salvage chemotherapy and are still not in FCM based MRD defined remission. iv. CD19 expression criteria: 1. CD19 tumor expression in bone marrow (BM) or peripheral blood (PB) within 3 months of study entry. 2. B-lineage of blast and expression of CD19 should be established. 3. There should be no other detectable clone that does not express CD19. 4. Absence of CD19 negative subclone of any type at time of study entry. b. Host Criteria: i. Age criteria: Age 3 years to less than 25 completed years at screening for enrolment on the study. ii. Fitness criteria: a. Adequate organ function. Clinically assessed, with further investigation if clinically indicated. This will include but not limited to those with severe systemic compromise of any major organ system as assessed by ejection fraction of iii. For males or females of reproductive potential, has agreed to use effective contraception method during the study for minimum 6 months after study treatment.
Exclusion criteria
Exclusion criteria: a. Failure to meet any of the inclusion criteria b. Patients who test positive on urine pregnancy testing and are pregnant or are lactating c. Isolated extra-medullary relapse d. Concomitant genetic syndromes associated with bone marrow failure states such as Fanconi anemia, Kostmann syndrome, Schwachmann syndrome or any other BM failure syndromes with the exception of Downs syndrome. e. Any syndrome with genetic predisposition to cancer eg. Li Fraumeni syndrome f. Any prior malignancy g. Active or latent hepatitis B or active hepatitis C detected at screening. Any test in the preceding 8 weeks will be considered valid h. Any uncontrolled infection at time of screening. i. Positive HIV test at screening. j. Grade II to IV graft-versus-host-disease (GVHD) for post Allo-SCT patients. k. Receiving an investigational medicinal product within 30 days of screening. l. Medications or treatments that will be excluded: • Corticosteroids within 72 hours of HCAR19 T-cell infusion, with the exception of physiologic replacement. • Allogeneic cellular therapy, such as donor lymphocyte in fusion within 6 weeks prior to infusion • Any ongoing GVHD therapies • Chemotherapy stopped prior to lymphodepletion based on clearance • CNS prophylaxis treatment m. Active CNS disease, whether established clinically, radiologically, or by CSF studies. Exception would be CNS 2 disease i.e. CSF containing blasts, but < 5 WBCs/microliter. Such patients, with no other evidence of CNS involvement would be eligible).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| i. To find the Phase 2 Dose P2D of HCAR19 in patients with relapsed refractory B ALL aged to 25 years. ii. To demonstrate efficacy of HCAR19 T cells in patients to 3 to 25 years of age with relapsed refractory B Cell ALL by Day 30 Bone Marrow Flow Cytometry Response iii. To establish safety and efficacy of HCAR19 when used as above.Timepoint: i. Day 30 Bone Marrow Response by Morphology and Flow Cytometry ii. Best Bone Marrow Flow Cytometry Response by Day 90 iii. Early Toxicities till Day 30 iv. Late Toxicities Beyond Day 30 till on follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| i. To study the persistence, expansion and phenotype of HCAR19 T-cells in the target tissues (blood, bone-marrow, cerebrospinal fluid (CSF), and other extramedullary sites if involved. ii. To study cytokine level and other biomarkers of toxicity and efficacy of infused HCAR19 T cells. To correlate toxicities, efficacy and biomarkers profile with steps and protocols of manufacturing HCAR19T cells.Timepoint: i. Early Dynamics till Day-30 ii. Subsequent Dynamics beyond Day- 30 till on follow-up | — |
Countries
India
Contacts
Public ContactDr Gaurav Narula
Tata Memorial Centre
Outcome results
None listed