Allo CART-19 Protocol

NCT ID: NCT01551043

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2016-06-30

Brief Summary

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).

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.

Conditions

Acute Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Group Type: EXPERIMENTAL

CART-19

Intervention Type: BIOLOGICAL

Interventions

CART-19

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Porter, MD

Role: PRINCIPAL_INVESTIGATOR

Abramson Cancer Center at Penn Medicine

Locations

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

UPCC 01410

Identifier Type: -

Identifier Source: org_study_id