Health Condition 1: C851- Unspecified B-cell lymphoma
Conditions
Interventions
Intervention1: HCAR19 cells: At IIT-Bombay, a novel and indigenous HCAR19 cell product has been designed and developed.
The gene therapy product (GTP) has been tested for the ex vivo and in vivo funct
Sponsors
Tata Memorial Hospital Research Administrative Council
Eligibility
Inclusion criteria
Inclusion criteria: a) Able to give written informed consent. b) Age greater than or equal to 18 years c) Histologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, or transformed follicular lymphoma. d) Chemotherapy refractory disease, as defined in the SCHOLAR-1 Study-This includes: Patients whose best response to the last chemotherapy regimen was progressive disease or stable disease lasting less than or equal to 6 months. e) Disease progression or recurrence f) Patients must have received an anti-CD20 monoclonal antibody and an anthracycline containing regimen. Patients with transformed follicular lymphoma, must have been treated for follicular lymphoma and have refractory disease after transformation. g) Measurable Disease as per International Working Group Response Criteria) h) Patient who is not willing or not feasible to undergo ASCT. i) Patient life expectancy greater than or equal to 12 weeks. j) Eastern Cooperative Oncology Group performance status of either 0 or 1 at the time of screening. k) Adequate organ function: l) Renal function - a serum creatinine of less than or equal to 1.5 Ã? upper limit of normal (ULN) or an estimated glomerular filtration rate greater than or equal to 60 mL/min/1.73 m2. m) Liver function- Alanine Aminotransferase n) A minimum level of pulmonary reserve, defined as grade less than or equal to 1 dyspnoea and pulse oxygenation greater than 91% on room air. o) Hemodynamically stable and left ventricular ejection fraction greater than or equal to 45% confirmed by echocardiogram or multiple-gated acquisition scan. p) No evidence of pericardial effusion. q) Adequate bone marrow reserve without transfusions, defined as absolute neutrophil count greater than 1000/mm3, platelets greater than or equal to 50,000/mm3, and haemoglobin greater 8.0g/dl r) Sexually active patients (women of childbearing potential) are required to use highly effective methods of contraception for at least 12 months following CAR T cell infusion.
Exclusion criteria
Exclusion criteria: a) Previous treatment with specific anti-CD19/anti-CD3 therapy or any other anti-CD19 directed therapy. b) Prior CAR-T cell therapy. c) Active central nervous system involvement by malignancy. d) Prior allogeneic HSCT. e) Investigational medicinal product within 30 days before screening. f) Use of following medications to be assessed for subject eligibility: • Steroid should be stopped greater than 72 hours before leukapheresis and CAR T cell infusion (less than 12 mg/m2/day of hydrocortisone or equivalent is allowed) • Immunosuppressive medication has to be stopped greater than or equal to 2 weeks before leukapheresis and cell infusion. • Any anti proliferative therapies other than lymphodepleting chemotherapy within 2 weeks of leukapheresis and 2 weeks before infusion to be stopped • Short-acting drugs used to treat leukaemia or lymphoma (i.e., tyrosine kinase inhibitors, and hydroxyurea), have to be stopped greater than 72 hours before leukapheresis and before cell infusion. • Other cytotoxic drugs, including low-dose daily or weekly maintenance chemotherapy, can be given within 2 weeks before leukapheresis and within 2 weeks before cellular infusion. • Antibodies, including anti-CD20 therapy, not to be used within 4 weeks before infusion or 5 half-lives of the respective antibody, whichever was longer • Central nervous system disease prophylaxis, has to be stopped greater than 1 week before cellular infusion (i.e., intrathecal methotrexate) • Prior radiation therapy within 2 weeks of infusion. g) Active replication of prior infection with hepatitis B or active hepatitis C (HCV RNA positive) h) HIV-positive patients i) Uncontrolled acute life-threatening bacterial, viral, or fungal infection (i.e., blood culture positive less than or equal to 72 hours before infusion) j) Unstable angina and/or myocardial infarction within 6 months before screening k) Previous or concurrent malignancies. Except in the case of adequately treated basal cell or squamous cell carcinoma, in situ carcinoma of the cervix or breast (treated curatively and without evidence of recurrence for greater than or equal to 3 years before study), or primary malignancy which has been completely resected and in complete remission for greater than or equal to 5 years l) Currently pregnant or lactating female subjects. m) A positive serum or urine pregnancy test performed within 24 hours before lymphodepletion n) Intolerance of the excipients of the CAR T cell product o) Cardiac arrhythmia not controlled with medical management P) Prior treatment with any adoptive T-cell therapy p) Active neurological autoimmune or inflammatory disorders.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To study the safety of CAR-T cell therapy in DLBCL. Study-related AE includes NCI CTC greater than or equal to Grade 3 signs or symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment, in the time-period between CAR-T infusion till week 24.These toxicities include, but are not limited to- Infusional toxicity, cytokine-release syndrome, macrophage activation syndrome, fever, hepatic dysfunction, cytopenias, rash, pulmonary toxicities.Timepoint: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in the cytokines and other soluble factors will be measured at different time pointsTimepoint: Day 7, Day 10, Day 14, Day 21, Day 28, 3 months;Development of host immune response to CART cellsTimepoint: 3 months, 6 months;Engraftment of CAR-T cellsTimepoint: Day 1, Day 2, Day 3, 1 month, 3 month, 6 month;Late complicationsTimepoint: 2 year, 5 year, 10 year;Manufacturing feasibility assessmentTimepoint: minus week 5;Objective Response RateTimepoint: 3 months;Overall Survival and Event fee survivalTimepoint: 2 year;To evaluate the phenotype and functional aspects of CART cells using multi-parametric flow cytometryTimepoint: 3 months, 6 months | — |
Countries
India
Contacts
Public ContactDr Hasmukh Jain
Tata Memorial Centre
Outcome results
None listed