Administration of T Lymphocytes for Prevention of Relapse of Lymphomas

Summary

Participation Requirements

Description

STUDY OBJECTIVES Primary Objective To determine the safety and tolerability and to estimate the MTD of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse Secondary Objectives To measure the survival of ATLCAR.CD30 in vivo To estimate PFS after infusion of ATLCAR.CD30 post...

STUDY OBJECTIVES Primary Objective To determine the safety and tolerability and to estimate the MTD of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse Secondary Objectives To measure the survival of ATLCAR.CD30 in vivo To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse To determine the overall survival after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma at high risk for relapse Exploratory Objective To measure patient-reported symptom, physical function, and health-related quality of life at baseline and over time in patients treated with ATLCAR.CD30 cells. ENDPOINTS Primary Endpoint Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and CRS toxicity will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of dose-limiting toxicity Secondary (Clinical) Endpoint PFS is defined from day of ASCT to relapse (in subjects with a documented complete response after ASCT) or progression (in subjects with documented stable disease or partial response after ASCT), or death as a result of any cause as per the Revised Response Criteria for Malignant Lymphoma. Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples. Exploratory Endpoint Patient reported symptoms will be measured using selected symptoms from the NCI PRO-CTCAE. Patient-reported physical function will be measured using the PROMIS Physical Function Score derived from the PROMIS Physical Function Short Form 20a v1.0. Patient-reported health-related quality of life will be measured using the PROMIS Global Health Score derived from the PROMIS Global Health Short Form v1.0-1.1. OUTLINE Patients scheduled to undergo an autologous stem cell transplantation (ASCT) for treatment of lymphoma will be approached for consent to screening and potential enrollment into LCCC1524. Peripheral blood cells will be collected from consenting patients who meet eligibility for cell procurement for creation of ATLCAR.CD30 cells prior to ASCT. The ASCT, including mobilization and collection of PBSCs, administration of myeloablative therapy, reinfusion of PBSCs and supportive care following transplant will be as per routine standard of care, and not expected to be impacted by enrollment into LCCC1524. Post ASCT, patients who meet eligibility criteria for treatment will receive one infusion of ATLCAR.CD30 cells once there is evidence of hematologic recovery. Research personnel will keep track of any patients who undergo procurement but do not undergo treatment with ATLCAR.CD30 cells, and the reason for withholding treatment. Cell Procurement Peripheral blood, up to 300 mL total (in up to 3 collections) will be obtained for subjects for cell procurement. In patients with low (CD3 count as assayed by flow cytometry less than 200/?l) T-cell count in the peripheral blood, a leukopheresis may be performed to isolate sufficient T cells. The parameters for pheresis will be up to 2 blood volumes. For pediatric patients (patients under 18 years of age), the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon per 2.2 lbs. that the child weighs. ATLCAR.CD30 Cells Administration Post ASCT, once the patient has started to experience hematologic recovery (defined as ANC ?500 cells/mm3 for 3 consecutive days, AND platelet count ?25 cells/mm3 without transfusion over the preceding 5 days, AND Hg ?8g/dL without transfusion support over preceding 5 days), ATLCAR.CD30 cells will be admnistered. This will generally occur between 14 and 20 days following infusion of autologous stem cells following high-dose chemotherapy. Duration of Therapy Therapy in LCCC1524 involves just one infusion of ATLCAR.CD30 cells. Treatment with one infusion will be administered unless: Patient decides to withdraw from study treatment, OR General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator. Duration of Follow-Up Patients will be followed for up to 15 years or until death, whichever occurs first. Patients removed from study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

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