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

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin's Lymphoma	Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan; Biological: Pegfilgrastim; Biological: 19-28z T CELLS; Procedure: Autologous Stem Cell Transplantation	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	17 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	April 2013
Estimated Primary Completion Date :	April 2019
Estimated Study Completion Date :	April 2019

Arms and Interventions

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Arm	Intervention/treatment
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.	Drug: Carmustine Drug: Etoposide Drug: Cytarabine Drug: Melphalan Biological: Pegfilgrastim Biological: 19-28z T CELLS Procedure: Autologous Stem Cell Transplantation

Outcome Measures

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Primary Outcome Measures :

1. 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
2. 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

Secondary Outcome Measures :

1. 2 year progression-free (PFS) [ Time Frame: 2 years ]
2. overall survival (os) [ Time Frame: 2 years ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

Principal Investigator:	Craig Sauter, MD	Memorial Sloan Kettering Cancer Center

More Information

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Additional Information:

Memorial Sloan Kettering Cancer Center 

Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT01840566 History of Changes
Other Study ID Numbers:	12-117
First Posted:	April 25, 2013
Last Update Posted:	April 18, 2018
Last Verified:	April 2018

Keywords provided by Memorial Sloan Kettering Cancer Center:

Relapsed; Refractory; Autologous Stem Cell Transplantation	HIGH DOSE CHEMOTHERAPY; 19-28z T cells/kg; 12-117

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Etoposide; Cytarabine; Melphalan; Carmustine; Antineoplastic Agents, Phytogenic; Antineoplastic Agents	Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists