CD19 Redirected Autologous T Cells

This study has been completed.
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: October 10, 2014
Last verified: October 2014

December 10, 2012
October 10, 2014
December 2012
July 2014   (final data collection date for primary outcome measure)
Number of Adverse Events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01747486 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
CD19 Redirected Autologous T Cells
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)

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL
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 1-5x10e8
    Arm 1: Target dose of 1-5x10e8 CART-19 cells (calculated as range of 10-50% transduced cells in 1 x10e9 total cells)
    Intervention: Biological: CART-19
  • 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)
    Intervention: Biological: CART-19
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
34
July 2014
July 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01747486
UPCC 03712
Yes
Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Not Provided
Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP