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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 1

Conditions: Non-Hodgkin's Lymphoma

Treatments: Drug: Melphalan; Biological: Pegfilgrastim; Drug: Cytarabine; Drug: Etoposide; Drug: Carmustine; Procedure: Autologous Stem Cell Transplantation; Biological: 19-28z T CELLS

Study type: Interventional

Funder types: Other

Identifiers

NCT01840566

12-117

Details and patient eligibility

About

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).

Enrollment: 17 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

HIGH DOSE CHEMOTHERAPY AND ASCT

Experimental group

Description:

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.

Treatment:

Biological: 19-28z T CELLS

Procedure: Autologous Stem Cell Transplantation

Drug: Etoposide

Drug: Carmustine

Drug: Cytarabine

Biological: Pegfilgrastim

Drug: Melphalan