Health Condition 1: C91- Lymphoid leukemia
Conditions
Interventions
Intervention1: Anti CD19 CAR- T Cells: 1 day Intravenous infusion of CD19-CAR T-cells
dosing ranges of 0.2 x 106 transduced cells/kilogram to 5 x 106 transducedcells/kilogram with acceptable rates of
Sponsors
Christian Medical College
Eligibility
Inclusion criteria
Inclusion criteria: 1. Subjects must have relapsed or refractory CD19 positive ALL or lymphoma, treated with at least two lines of therapy for lymphomas. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen. Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs). Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti- CD20 monoclonal antibody. Subjects with transformed FL, MZL, or CLL/SLL must have progressed, had SD or recurred with transformed disease after initial treatment for DLBCL. Subjects who relapse =12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant. 2. The patient’s disease must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available. 3. Age = 2 years. Performance status: Performance Status: Adult Subjects: ECOG = 2; Subjects > 10 years of age: Karnofsky = 80%; Subjects = 10 years of age: Lansky scale = 80% Normal Organ and Marrow Function (supportive care is allowed per institutional standards) 4. Total bilirubin = 1.5 ULN o AST(SGOT) = 3 times ULN o ALT(SGPT) = 3 times ULN o Serum Creatinine = 1.5mg% o Subjects must have the following hematologic function parameters: 5. ANC > 1000, Platelets > 50,000 6. 7. At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives. 8. Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
Exclusion criteria: 1. Autologous transplant within 6 weeks of planned CAR-T cell infusion. 2. History of allogeneic stem cell transplant. 3. Recipient of CAR-T cell therapy outside of this protocol. 4. Active central nervous system or meningeal involvement by tumor. Subjects with untreated brain metastases/CNS disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration. 5. History of active malignancy other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast). 6. Active HIV infection. 7. Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements. 8. Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four (4) months after receiving the preparative regimen. 9. Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy 10. Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 2 X 106 cells/kilogram Incidence and severity of adverse events, DLTs, MTDTimepoint: 30 days and long term follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Complete response (CR) rate one-month post infusion in subjects with ALL and CR rate at three months post infusion in subjects with leukemia and lymphoma respectively MRD status one-month post infusion Overall and event free survival at one yearTimepoint: 30 days 12 months | — |
Countries
India
Contacts
Public ContactVikram Mathews
Christian Medical College
Outcome results
None listed