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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

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ClinicalTrials.gov Identifier: NCT01840566
Recruitment Status : Active, not recruiting
First Posted : April 25, 2013
Last Update Posted : April 18, 2018
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

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, Older Adult)
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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01840566


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  This link exits the ClinicalTrials.gov site

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    Key Record Dates
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