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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01840566
First received: April 23, 2013
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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 Intervention 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 Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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:
  • 2 year progression-free (PFS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • overall survival (os) [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: April 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Transplant eligible patients will be eligible if criteria met per below.

Inclusion Criteria:

  • Patients > or = to 18 years of age with aggressive B-cell non-Hodgkin lymphoma subtypes including, but not limited to, relapsed or refractory diffused large B-cell lymphoma (DLBCL), Burkitt's lymphoma or transformed indolent B-cell non-Hodgkin lymphoma (including chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) 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, 1999 IWG criteria (section 12.2 and 12.383).
  • Creatinine < or = 1.5 mg/100 ml (or measured 24 hour creatinine clearance of > or = to 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,
  • Granulocytes >1,000/mm3, platelets >50,000/mm3, hemoglobin >8.0g/dl.
  • 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 < or = to 70 (see appendix VI).
  • Patients previously treated with 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01840566

Contacts
Contact: Craig Sauter, MD 212-639-3460
Contact: Jenna Goldberg, MD 212-639-4828

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Craig Sauter, MD    212-639-3460      
Contact: Jenna Goldberg, MD    212-639-4828      
Principal Investigator: Craig Sauter, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Craig Sauter, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01840566     History of Changes
Other Study ID Numbers: 12-117
Study First Received: April 23, 2013
Last Updated: June 12, 2014
Health Authority: United States: Food and Drug Administration

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
Carmustine
Melphalan
Cytarabine
Etoposide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 28, 2014