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
- Conditions
- Interventions
- Registration Number
- NCT01840566
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 17
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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).
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Creatinine ≤ 1.5 mg/100 ml (or measured 24 hour creatinine clearance of ≥ 50 cc/min)
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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,
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Adequate cardiac function (LVEF>40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment.
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Adequate pulmonary function as assessed by DLCO of > or = to 45% adjusted for hemoglobin.
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Life expectancy of > 3 months.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HIGH DOSE CHEMOTHERAPY AND ASCT Pegfilgrastim 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. HIGH DOSE CHEMOTHERAPY AND ASCT Autologous Stem Cell Transplantation 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. HIGH DOSE CHEMOTHERAPY AND ASCT 19-28z T CELLS 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. HIGH DOSE CHEMOTHERAPY AND ASCT Carmustine 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. HIGH DOSE CHEMOTHERAPY AND ASCT Etoposide 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. HIGH DOSE CHEMOTHERAPY AND ASCT Cytarabine 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. HIGH DOSE CHEMOTHERAPY AND ASCT Melphalan 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.
- Primary Outcome Measures
Name Time Method maximum tolerated dose (MTD) 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 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
Name Time Method overall survival (os) 2 years 2 year progression-free (PFS) 2 years
Trial Locations
- Locations (7)
Memorial Sloan Kettering Commack (Limited protocol activities)
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Nassau (Limited protocol activites)
🇺🇸Rockville Centre, New York, United States
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
🇺🇸Montvale, New Jersey, United States
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth (Limited protocol activities)
🇺🇸Middletown, New Jersey, United States