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

• ClinicalTrials.gov Identifier: NCT01840566
• Recruitment Status: Active, not recruiting
• First Posted: April 25, 2013
• Last Update Posted: April 8, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

Tracking Information

• First Submitted Date: April 23, 2013
• First Posted Date: April 25, 2013
• Last Update Posted Date: April 8, 2022
• Study Start Date: April 2013
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 23, 2013)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 23, 2013)

• 2 year progression-free (PFS) [ Time Frame: 2 years ]
• overall survival (os) [ Time Frame: 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Hodgkin's Lymphoma

Intervention

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

Study Arms

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.

Interventions:

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

Publications *

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
• Sauter CS, Senechal B, Riviere I, Ni A, Bernal Y, Wang X, Purdon T, Hall M, Singh AN, Szenes VZ, Yoo S, Dogan A, Wang Y, Moskowitz CH, Giralt S, Matasar MJ, Perales MA, Curran KJ, Park J, Sadelain M, Brentjens RJ. CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. Blood. 2019 Aug 15;134(7):626-635. doi: 10.1182/blood.2018883421. Epub 2019 Jul 1.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 26, 2016): 17
• Original Estimated Enrollment (submitted: April 23, 2013): 18
• Estimated Study Completion Date: April 2023
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01840566
• Other Study ID Numbers: 12-117
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Memorial Sloan Kettering Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Memorial Sloan Kettering Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mark Geyer, MD; Memorial Sloan Kettering Cancer Center

• PRS Account: Memorial Sloan Kettering Cancer Center
• Verification Date: April 2022