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 ongoing, but not recruiting participants.
Sponsor:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01840566
First Posted: April 25, 2013
Last Update Posted: April 27, 2017
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
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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: | 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 |
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 ]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
Secondary Outcome Measures:
- 2 year progression-free (PFS) [ Time Frame: 2 years ]
- overall survival (os) [ Time Frame: 2 years ]
| Enrollment: | 17 |
| Study Start Date: | April 2013 |
| Estimated Study Completion Date: | April 2018 |
| Estimated Primary Completion Date: | April 2018 (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
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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
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
Additional Information:
| Responsible Party: | Memorial Sloan Kettering Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01840566 History of Changes |
| Other Study ID Numbers: |
12-117 |
| First Submitted: | April 23, 2013 |
| First Posted: | April 25, 2013 |
| Last Update Posted: | April 27, 2017 |
| Last Verified: | April 2017 |
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 |