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

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
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.

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
HIGH DOSE CHEMOTHERAPY AND ASCTPegfilgrastimThis 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 ASCTAutologous Stem Cell TransplantationThis 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 ASCT19-28z T CELLSThis 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 ASCTCarmustineThis 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 ASCTEtoposideThis 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 ASCTCytarabineThis 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 ASCTMelphalanThis 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
NameTimeMethod
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

safety2 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
NameTimeMethod
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

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