Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL

Summary

Participation Requirements

Description

STUDY OBJECTIVES Primary Objective (Phase Ib portion of Study) To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). To establish a safe do...

STUDY OBJECTIVES Primary Objective (Phase Ib portion of Study) To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). To establish a safe dose (ie, number cells/m2) of ATLCAR.CD30 to infuse after lymphodepletion with bendamustine and fludarabine in pediatric patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Primary Objective (Phase II portion of study) To estimate 2 year progression free survival (PFS) after administration of ATLCAR.CD30 in combined adult/pediatric patients with CD30+ refractory/relapsed HL and NHL Secondary Objectives To estimate 2 year overall survival (OS) after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL. To estimate 2 year OS after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL. To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine in adult patients with CD30+ refractory/relapsed HL and NHL. To estimate 2 year PFS after administration of ATLCAR.CD30 following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ refractory/relapsed HL and NHL. To estimate the objective response rate as defined by the Lugano Classification78 for CAR.CD30 transduced ATL following lymphodepletion with bendamustine when administered in adult patients with CD30+ relapsed/refractory HL and NHL. To estimate the objective response rate as defined by the Lugano Classification78 for CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL. To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine in adult patients with CD30+ relapsed/refractory HL and NHL To estimate duration of response after administration of CAR.CD30 transduced ATL following lymphodepletion with bendamustine and fludarabine in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL To further describe the adverse events associated with CAR.CD30 transduced ATL when administered in adult and pediatric patients with CD30+ relapsed/refractory HL and NHL. To evaluate the safety of bendamustine alone or combined with fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATL in adult patients. To evaluate the safety of bendamustine and fludarabine as lymphodepleting agents prior to infusion of CAR.CD30 transduced ATLs in pediatric patients. To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine. To measure the survival of ATLCAR.CD30 in vivo when infused after lymphodepletion with bendamustine and fludarabine. To measure patient-reported symptom, physical function, and health-related quality of life at baseline and over time in adult patients treated with CAR.CD30 T cells. Primary Endpoint (Phase Ib) Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and Cytokine Release Syndrome (CRS) toxicity will be graded according to the CRS Management Guidelines and CRS Toxicity Grading Scale Primary Endpoint (Phase II) PFS is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification Secondary Endpoints Overall survival will be measured from the date of administration of CAR.CD30 transduced ATL to date of death and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion. Progression free survival is defined from day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at time of cell infusion) or progression (in patients without complete response at time of cell infusion), or death as a result of any cause per the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion. The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) as determined by the Lugano classification78 and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion. The duration of response will be defined as time from documentation of tumor response to disease progression and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion. Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0). S Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow cytometry in peripheral blood samples and will be measured separately in subjects receiving bendamustine alone for lymphodepletion and those receiving a combination of bendamustine and fludarabine for lymphodepletion. For adult patients: 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 Cell Procurement Up to 100 mL per collection (up to 3 collections) of peripheral blood will be obtained from patients 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 2 blood volumes. ATLCAR.CD30 Cells Administration ATLCAR.CD30 cells will be administered as described below 1-14 days (preferably 1-2 days) after lymphodepletion with bendamustine and fludarabine. ATLCAR.CD30 cells will be given by a licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. Patients with a partial response or stable disease at 6 weeks may receive a second infusion of ATLCAR.CD30 if cells are available. Note: Lymphodepletion with bendamustine and fludarabine will occur for three consecutive days and may be given prior to a second infusion of cells (if applicable). Duration of Therapy Therapy in Lineberger Comprehensive Cancer Center (LCCC) 1532 involves 1-2 infusions 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 for Replication Competent Retrovirus (RCR) evaluation 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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