Allo CART-19 Protocol

July 7, 2020 updated by: University of Pennsylvania

Pilot Study of Donor Lymphocyte Infusions Using Donor T Cells Engineered to Contain Anti-CD19 Attached To TCR And 4-1BB Signaling Domains in Patients With Relapsed CD19+ All After Allogeneic Stem Cell Transplantation

The primary objective is to determine the safety and survival of the redirected allogeneic T cells transduced with the anti-CD19 lentiviral vector (referred to as CART-19 cells).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The investigators propose an open label, single center, pilot study to evaluate the safety and tolerability, and persistence of donor lymphocytes engineered to express a chimeric antigen receptor targeting CD19 which is linked to the CD3:4-1BB signaling chains in patients with CD19+ acute lymphoblastic leukemia (ALL). Upon enrollment, donors will undergo leukapheresis and patients will undergo an optional bone marrow/lymph node biopsy approximately four weeks prior to dosing. Between dosing and treatment, patients may undergo an additional chemotherapy treatment depending upon their disease. At dosing, patients will receive redirected donor lymphocytes targeted against CD19 (allo-CART-19 cells). The cell dose will be given as a split infusion over three days to enhance the ability to manage any infusion related toxicity. Patients will be monitored weekly for four weeks. At the end of four weeks, patients will undergo a second leukapheresis and second optional bone marrow/lymph node biopsy. At this point the patient will also undergo restaging. Observation and monitoring of patients will continue on a monthly basis until week 24 post dosing. Annual follow-up for lentiviral vector safety will be carried out for 15 years in accordance with FDA guidelines for retroviral vectors. Ten subjects will be targeted for this study, with an expected rate of drop out of 30% due to disease progression between enrollment and week four post dosing.

Study Type

Interventional

Enrollment (Actual)

2

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

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Abramson Cancer Center of the University of Pennsylvania

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • CD19+ ALL relapsed after allogeneic SCT.
  • No active GVHD and off immunosuppression for greater than or equal to 4 weeks.
  • Age greater than or equal to 18 years.
  • Creatinine less than or equal to2.5 mg/dl.
  • ALT/AST less than or equal to3x normal
  • Bilirubin less than or equal to2.0 mg/dl
  • Donor is available and is able to undergo apheresis. A separate donor consent process and form is described below.
  • Voluntary informed consent is given.

Exclusion Criteria:

  • Pregnant or lactating women. The safety of this therapy on unborn children is not known. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
  • Uncontrolled active infection.
  • Active hepatitis B or hepatitis C infection.
  • Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
  • Previously treatment with any gene therapy products.
  • Feasibility assessment during screening demonstrates less than 30% transduction of target lymphocytes, or insufficient expansion ( less than 5-fold) in response to CD3/CD28 costimulation..
  • Any uncontrolled active medical disorder that would preclude participation as outlined.
  • HIV infection.
  • Patients with active CNS involvement with leukemia. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was greater than or equal to 4 weeks before enrollment
  • Patients with active GVHD or requiring immune suppression.

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: Arm 1
Biological: CART-19

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of Adverse Events
Time Frame: 26 months
26 months

Collaborators and Investigators

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

Sponsor

University of Pennsylvania

Investigators

  • Principal Investigator: David Porter, MD, Abramson Cancer Center of the University of Pennsylvania

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

September 1, 2010

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

March 8, 2012

First Submitted That Met QC Criteria

March 9, 2012

First Posted (Estimate)

March 12, 2012

Study Record Updates

Last Update Posted (Actual)

July 9, 2020

Last Update Submitted That Met QC Criteria

July 7, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UPCC 01410

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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