CD19 Redirected Autologous T Cells

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01747486
First received: December 10, 2012
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

This is a randomized, open-label, parallel group study to determine the optimal dose of CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR Zeta and 4-1 BB co-stimulatory domains) of the two dose levels being assessed (1-5x10e8 vs. 1-5x10e7 CART-19 cells). This trial will be conducted in two stages.


Condition Intervention Phase
Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL
Biological: CART-19
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dose Optimization Trial of Autologous T Cells Engineered to Express Anti-CD19 Chimeric Antigen Receptor (CART-19) in Patients With Relapsed or Refractory CD19+ Chronic Lymphocytic Leukemia (CLL)

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 32
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Target dose of 1-5x10e8
Arm 1: Target dose of 1-5x10e8 CART-19 cells (calculated as range of 10-50% transduced cells in 1 x10e9 total cells)
Biological: CART-19
CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR zeta and 4-1BB costimulatory domains)
Experimental: Target dose of 1-5x10e7
Arm 2: Target dose of 1-5x10e7 CART-19 cells (calculated as the range of 10-50% transduced cells in 1 x10e8 total cells)
Biological: CART-19
CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR zeta and 4-1BB costimulatory domains)

Detailed Description:

This study is being conducted to determine the optimal dose of autologous CART-19 T cells engineered to express anti-CD19 chimeric antigen receptors in patients with relapsed or refractory CD19 positive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The two dose levels being assessed are 1-5x10e8 versus 1-5x10e7. The trial will be conducted in two stages. In stage I subjects will be randomized into one of the two dose cohort with a1:1 ratio for a total of 12 subjects per dose cohort. Stage II will be to enroll an additional 8 subjects to the selected dose cohort once safety, tolerability and clinical responses have been evaluated to determine the optimal dose cohort.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented CD19+ CLL or SLL
  • Successful test expansion of T-cells (as described in Section 6.1)
  • At least 2 prior chemotherapy regimens. At least one fludarabine or other nucleoside analog containing regimen. Chemotherapy in combination with monoclonal antibody (Rituxan) will be considered one prior regimen, but single agent Rituxan will not be considered one prior regimen. Single agent ofatumumbab will be counted as a regimen.
  • Less than 2 years between last therapy and progression (e.g. most recent progression free interval 2 years)
  • Subject has no available or declines curative treatment options such as allogeneic SCT and has limited prognosis (2 years survival) with currently available therapies
  • Expected survival 12 weeks
  • Performance status (ECOG) 0 or 1
  • Age greater than or equal to 18 years
  • Adequate organ system function including:

    1. Creatinine 1.6 mg/dl
    2. ALT/AST 3x upper limit of normal
    3. Direct Bilirubin 2.0 mg/dl
  • Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy
  • Patients with relapsed disease after prior allogeneic SCT (myeloablative or nonmyeloablative) will be eligible if they meet all other inclusion criteria and:

    1. experienced graft rejection (no evidence of donor cells by STR analysis on 2 occasions separated by at least 1 month)
    2. Have no active GVHD and require no immunosuppression
    3. Are more than 6 months from transplant
  • No contraindications for leukapheresis
  • Gives voluntary informed consent

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.
  • Any uncontrolled active medical disorder that would preclude participation as outlined
  • HIV infection
  • Patients with active CNS involvement with malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was 4 weeks before enrollment.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01747486

Contacts
Contact: Holly McConville, RN 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramsonc Cancer Center of The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Holly McConville, RN    855-216-0098    PennCancerTrials@emerigingmed.com   
Principal Investigator: Noelle Frey, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01747486     History of Changes
Other Study ID Numbers: UPCC 03712
Study First Received: December 10, 2012
Last Updated: December 11, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014