High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma

Tracking Information
First Submitted Date ICMJE	April 23, 2013
First Posted Date ICMJE	April 25, 2013
Last Update Posted Date	April 18, 2018
Study Start Date ICMJE	April 2013
Estimated Primary Completion Date	April 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 23, 2013)	maximum tolerated dose (MTD) [ Time Frame: 2 years ]will be assessed utilizing a standard 3+3 cell dose escalation to determine the maximum tolerated dose of CD19+ CAR T cells; safety [ Time Frame: 2 years ]Toxicity will be graded on a scale of 1 to 5 as described by the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01840566 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 23, 2013)	2 year progression-free (PFS) [ Time Frame: 2 years ]; overall survival (os) [ Time Frame: 2 years ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma
Official Title ICMJE	A Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma
Brief Summary	The purpose of this study is to test the safety of delivering the patients' own immune cells, called T cells, after the high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT).
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Non-Hodgkin's Lymphoma
Intervention ICMJE	Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Biological: Pegfilgrastim; Biological: 19-28z T CELLS; Procedure: Autologous Stem Cell Transplantation
Study Arms	Experimental: HIGH DOSE CHEMOTHERAPY AND ASCT; This is a phase 1 dose escalation study designed to determine the maximum tolerated dose (MTD) of CAR modified T cells in patients with relapsed and refractory aggressive B-NHL. Three dose levels (5 x 106 19-28z T cells/kg, 1 x 107 19-28z T cells/kg, and 2 x 107 19-28z T cells/kg) are considered for the MTD.; Interventions: Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Biological: Pegfilgrastim; Biological: 19-28z T CELLS; Procedure: Autologous Stem Cell Transplantation
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: April 26, 2016)	17
Original Estimated Enrollment ICMJE; (submitted: April 23, 2013)	18
Estimated Study Completion Date	April 2019
Estimated Primary Completion Date	April 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Transplant eligible patients will be eligible if criteria met per below. Inclusion Criteria: Patients ≥ 18 years of age with aggressive B-cell non-Hodgkin lymphoma subtypes including, relapsed or refractory diffused large B-cell lymphoma (DLBCL), and transformed follicular lymphoma meeting at least one of the following criteria: Bone marrow involvement at the time of relapse or refractory disease and not appropriate for allogeneic transplantation. PET positive disease outside of one radiation port unless single-port disease treated with prior radiotherapy within the port, following > or = to 2 cycles of salvage chemotherapy, still achieving chemosensitive status 1999 IWG criteria (section 12.2 and 12.383).; Creatinine ≤ 1.5 mg/100 ml (or measured 24 hour creatinine clearance of ≥ 50 cc/min); Bilirubin <2.0 mg/100 ml, AST and ALT <3x the upper-limit of normal, PT and PTT < 2x normal outside the setting of stable chronic anticoagulation therapy,; Adequate cardiac function (LVEF>40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment.; Adequate pulmonary function as assessed by DLCO of > or = to 45% adjusted for hemoglobin.; Life expectancy of > 3 months. Exclusion Criteria: Karnofsky performance status ≤ 70 (see appendix VI).; Patients with other aggressive B-cell malignancies including, but not limited to: Burkitt lymphoma, transformed CLL/SLL and transformed marginal zone lymphoma that are not included in 6.1 inclusion criteria.; Patients previously treated with autologous or allogeneic bone marrow or stem cell transplantation are ineligible.; Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study.; Uncontrolled bacterial, viral or fungal infection.; Patients with HIV, active hepatitis B or hepatitis C infection.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01840566
Other Study ID Numbers ICMJE	12-117
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Memorial Sloan Kettering Cancer Center
Study Sponsor ICMJE	Memorial Sloan Kettering Cancer Center
Collaborators ICMJE	Not Provided
Investigators ICMJE	Principal Investigator: Craig Sauter, MD Memorial Sloan Kettering Cancer Center
PRS Account	Memorial Sloan Kettering Cancer Center
Verification Date	April 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP