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

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

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).

Study Overview

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack (Limited Protocol Activities)
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Rockville Centre, New York, United States, 11553
        • Memorial Sloan Kettering Nassau (Limited Protocol Activites)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
2 years
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
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
2 year progression-free (PFS)
Time Frame: 2 years
2 years
overall survival (os)
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Estimated)

April 1, 2024

Study Completion (Estimated)

April 1, 2024

Study Registration Dates

First Submitted

April 23, 2013

First Submitted That Met QC Criteria

April 23, 2013

First Posted (Estimated)

April 25, 2013

Study Record Updates

Last Update Posted (Actual)

May 25, 2023

Last Update Submitted That Met QC Criteria

May 24, 2023

Last Verified

May 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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