Health Condition 1: C833- Diffuse large B-cell lymphoma Health Condition 2: C820- Follicular lymphoma grade I Health Condition 3: C821- Follicular lymphoma grade II Health Condition 4: C823- Follicular lymphoma grade IIIa Health Condition 5: C824- Follicular lymphoma grade IIIb Health Condition 6: C831- Mantle cell lymphoma Health Condition 7: C859- Non-Hodgkin lymphoma, unspecified Health Condition 8: C91Z- Other lymphoid leukemia Health Condition 9: C851- Unspecified B-cell lymphoma
Conditions
Interventions
Intervention1: HCAR19 (2nd generation Anti-CD19-4-1BB-CD3? chimeric antigen receptor T-cell therapy): Autologous T-cells will be transduced using a lentiviral vector that will contain a gene coding fo
Sponsors
Immunoadoptive Cell Therapy Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: All the subjects must meet the Inclusion Criteria 1 to 12 High grade lymphoma subjects must additionally meet inclusion criteria 13 to 17 Other B Cell lymphoma subjects must additionally meet inclusion criteria 18 to 23 B ALL subjects must additionally meet inclusion criteria 24 to 28 1 Age 15 and above 2 ECOG 0 to 2 3 Life expectancy greater than or equal to 12 weeks 4 Renal Function Creatinine clearance (by Cockcroft Gault) greater than or equal to 60 cc per min (In the lymphoma cohort, patients can be enrolled if creatinine clearance is greater than or equal to 30 cc per min In such instances Bendamustine will be used as a conditioning regimen) 5 Liver Function Serum ALT and AST less than or equal to 3 times ULN unless the derangements can be explained by underlying malignancy and Total bilirubin less than or equal to 2 times ULN , except in subjects with Gilberts syndrome or isolated unconjugated hyperbilirubinemia or unless the derangements can be explained by underlying malignancy 6 Hemodynamically stable and left ventricular ejection fraction greater than or equal to 45 percentage confirmed by echocardiogram or multiple gated acquisition scan 7 Baseline oxygen saturation greater 92 percent on room air 8 ANC greater than or equal to 500 per µL unless in the opinion of the PI cytopenia is due to underlying malignancy 9 Platelet count greater than or equal to 50,000 per µL unless in the opinion of the PI cytopenia is due to underlying malignancy 10 Females of childbearing potential must have a negative serum or urine pregnancy test 24 hours prior to conditioning therapy 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 12 Able to give written informed consent 13 Histologically confirmed previously treated DLBCL, PMBCL, or transformed follicular lymphoma, Follicular Lymphoma Grade 3 B and High grade B cell lymphoma 14 Patients with Chemotherapy refractory disease, as defined as following (a) Patients whose best response to the last chemotherapy regimen was progressive disease or stable disease (b) Disease progression or recurrence less than or equal to 12 months after ASCT (c) Relapsed disease defined as complete remission to first line therapy followed by biopsy proven disease relapse less than or equal to 12 months of initiating first line therapy (d) Relapsed disease beyond 12 months will be considered if auto SCT is not feasible 15 Patients who are not willing or not feasible to undergo ASCT 16 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 17 Measurable Disease as per International Working Group Response Criteria 18 Any of one of the following histology confirmed (a) Mantle Cell Lymphoma (b) Follicular Lymphoma Grade I to IIIA (c) Marginal Zone Lymphoma 19 Relapsed or refractory disease to prior therapy, defined by the following (Disease progression after last regimen, or Refractory disease is defined failure to achieve a PR or CR to the last regimen) (a) MCL Up to 5 prior regimens for MCL. Prior therapy must ha
Exclusion criteria
Exclusion criteria: All the subjects must meet the Exclusion Criteria 1 to 15 High grade lymphoma subjects must additionally meet exclusion criteria 16 to 23 Low grade lymphoma subjects must additionally meet exclusion criteria 24 to 27 B ALL subjects must additionally meet inclusion criteria 28 to 34 1. Prior CD19 targeted therapy with the 1. exception of subjects who received HCAR19 in this study and are eligible for re treatment. 2. Uncontrolled acute life threatening bacterial, viral, or fungal infection (i.e., blood culture positive=72 hours before infusion) 3. HIV positive patients 4. Active replication of prior infection with hepatitis B or active hepatitis C (HCV RNA positive) 5. Unstable angina and/or myocardial infarction within 6 months before screening 6. 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 =3 years 8. Currently pregnant or lactating female subjects. 9. Intolerance of the excipients of the CAR T cell product 10. Active neurological autoimmune or inflammatory disorders. 11. Primary immunodeficiency 12. Short acting drugs used to treat leukaemia or lymphoma (i.e., tyrosine kinase inhibitors, and hydroxyurea), have to be stopped more than 72 hours before leukapheresis and before cell infusion. 13. Patients with Burkitt’s lymphoma/leukemia 14. Steroid should be stopped more than 72 hours before leukapheresis and CAR T cell infusion (less than 12 mg/m2/day of hydrocortisone or equivalent is allowed) 15. In the investigators judgement, the subject is unlikely to comply with the study requirements for participation. 16. Active central nervous system involvement by malignancy. 17. Prior allogeneic HSCT 18. Immunosuppressive medication has to be stopped =2 weeks before leukapheresis and cell infusion. 19. Any anti proliferative therapies other than lymphodepleting chemotherapy should be stopped before 2 weeks of leukapheresis and 2 weeks before infusion. 20. Other cytotoxic drugs, including low dose daily or weekly maintenance chemotherapy, can be given 2 weeks before leukapheresis and before cellular infusion. 21. 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 22. Central nervous system disease prophylaxis, has to be stopped more than 1 week before cellular infusion (i.e., intrathecal methotrexate) 23. Prior radiation therapy before 2 weeks of infusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR)Timepoint: 1 month | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of response (DOR) lymphomaTimepoint: 2 years;Event Free Survival (EFS)Timepoint: 2 years;Overall Survival (OS)Timepoint: 2 years;Progression Free Survival(PFS)Timepoint: 2 years;Safety: Adverse Event of Special InterestTimepoint: 6 months | — |
Countries
India
Contacts
Public ContactDr Hasmukh Jain
Tata Memorial Hospital
Outcome results
None listed