Health Condition 1: C859- Non-Hodgkin lymphoma, unspecified
Conditions
Interventions
Intervention1: CAR-T cell therapy plus Nivolumab: Nivolumab (40mg), an immunotherapy will be administered once in 28 days for 6 cycles after completion of CAR-T cell therapy Day 28
Intervention2: CAR-
Sponsors
Dr Hasmukh Jain
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age more than equal to 18 years 2. Histologically confirmed diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell NHL. 3. Patient achieved Complete Response on day 28 response assessment post Actaly-cel infusion. The complete inclusion criteria is available in the protocol 4. Indication for CART1 Actaly cel first dose should be chemotherapy refractory disease defined as progressive or stable disease as the best response to the most recent chemotherapy regimen or disease progression or relapse within 12 months after autologous stem cell transplantation ASCT 5. Subject 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 6. Subject must have received CART1 Actaly cel first dose at a target dose of 5x10 to the power of 6, CAR T cells per Kg with 20 percent margin 7. Patient is not willing or not feasible to undergo ASCT 8. Patient life expectancy 12 weeks or more 9. Eastern Cooperative Oncology Group performance status of 0 to 2 at the time of screening 10. Adequate organ function at the time of screening a. Renal function a serum creatinine of 1.5 times upper limit of normal ULN or an estimated glomerular filtration rate 60 mL per min per 1.73 m2 or more b. Liver function Alanine Aminotransferase 2.5 times the ULN for age and gender and bilirubin 2.0 mg per dl or less unless the patient had Gilbert syndrome in which case they can be included if their total bilirubin is 5.0 times ULN or less and direct bilirubin is 1.5 times ULN or less c. A minimum level of pulmonary reserve defined as grade 1 or less dyspnea and pulse oxygenation more than 91 percent on room air d. Hemodynamically stable and left ventricular ejection fraction 45 percent or more confirmed by echocardiogram or multiple gated acquisition scan No evidence of pericardial effusion e. Adequate bone marrow reserve defined as absolute neutrophil count more than 1000 per mm3 platelets 50000 per mm3 or more and hemoglobin more than 8.0 g per dl 11. 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: 1. Grade 3 or 4 CRS, ICANS, IEC-HS from previous treatment with specific anti-CD19 or anti-CD3 therapy or any other anti-CD19 directed therapy. 2. Need for mechanical ventilation or vasopressors during the previous treatment with Actaly-cel 3. Active central nervous system involvement by malignancy. 4. Active replication of prior infection with hepatitis B or active hepatitis C HCV RNA positive or HIV positive patients 5. Uncontrolled acute life-threatening bacterial viral or fungal infection i.e. blood culture positive 72 hours before infusion 6. Unstable angina and or myocardial infarction within 6 months before screening or cardiac arrhythmia not controlled with medical management 7. 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 3 years before study or primary malignancy which has been completely resected and in complete remission for 5 years 8. Currently pregnant or lactating female subjects 9. Previous treatment with antibodies targeting immune checkpoint pathways such as anti PD 1 anti PD L1 anti CD137 or anti CTLA 4 or other agents that modulate T cell co-stimulation 10. Patients with active or known autoimmune diseases including immune colitis inflammatory bowel disease immune pneumonitis pulmonary fibrosis or psychiatric conditions including those within the past year will be excluded However patients with type 1 diabetes mellitus residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement or skin conditions e.g. vitiligo psoriasis or alopecia not requiring systemic treatment may be included 11. A history of severe hypersensitivity to the investigational product or any component of its formulation including severe reactions to monoclonal antibodies NCI CTCAE v5 Grade 3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival defined as the time from enrollment to disease recurrence, or death.Timepoint: At the end of 1-year | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) Acute and long-term toxicities CAR RQ PCR monitoring B and T-cell enumeration Timepoint: 1 year follow up | — |
Countries
India
Contacts
Public ContactHasmukh Jain
Tata Memorial Hospital
Outcome results
None listed