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Dose Optimization Trial of CD19 Redirected Autologous T Cells

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ClinicalTrials.gov Identifier: NCT01747486
Recruitment Status : Completed
First Posted : December 11, 2012
Results First Posted : February 26, 2019
Last Update Posted : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE December 10, 2012
First Posted Date  ICMJE December 11, 2012
Results First Submitted Date  ICMJE December 11, 2018
Results First Posted Date  ICMJE February 26, 2019
Last Update Posted Date August 30, 2019
Actual Study Start Date  ICMJE January 2, 2013
Actual Primary Completion Date December 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
Number of Patients Achieving Complete Response Within 3 Months [ Time Frame: 3 months ]
Complete response (including complete response with incomplete marrow recovery) within 3 months (in evaluable patients). The eveluable set comprise of patients who have received CART19 at intended dose level and completed at least 3-month follow-up after the infusion or discontinued due to disease progression, new cancer therapy or death.
Original Primary Outcome Measures  ICMJE
 (submitted: December 10, 2012)
Number of Adverse Events [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Optimization Trial of CD19 Redirected Autologous T Cells
Official Title  ICMJE 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)
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Patients Who Have Relapsed or Refractory CLL (3rd Line) or SLL
Intervention  ICMJE Biological: CART-19
CART-19 cells (autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR zeta and 4-1BB costimulatory domains)
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 25, 2019)
42
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2012)
32
Actual Study Completion Date  ICMJE April 6, 2018
Actual Primary Completion Date December 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Documented CD19+ CLL or SLL
  • Successful test expansion of T-cells
  • At least 2 prior chemotherapy regimens, not including single agent monoclonal antibody (rituxan) therapy. Single agent ofatumumab will be counted as a regimen. -Patients with high risk disease manifested by deletion chromosome 17p will be eligible if they fail to achieve a CR to initial therapy or progress within 2 years of 1 prior regimen.
  • Patients who progress within 2 years after the second or higher line of therapy will be eligible. For instance, patients who had progression < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible.
  • Subject is not appropriate candidate for a potentially curative allogeneic SCT due to the state of disease, co-morbid illness, lack of an available donor, or patient declines Performance status (ECOG) 0 or 1
  • Age >/= 18 years
  • Adequate organ system function including:

    1. Creatinine < 1.6 mg/dl
    2. ALT/AST < 3x upper limit of normal
    3. Total 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. Have no active GVHD and require no immunosuppression
    2. Are more than 6 months from transplant
  • No contraindications for leukapheresis
  • Left Ventricular Ejection fraction >40%
  • Gives voluntary informed consent

Retreatment Inclusion Criteria

  • Performance Status 0-1
  • Adequate organ system function including:

    • Creatinine < 1.6 mg/dl
    • ALT/AST < 3x upper limit of normal
    • Total Bilirubin < 2.0 mg/dl
  • Subject is not an appropriate candidate for a potentially curative allogeneic SCT due to the state of disease, co-morbid illness, lack of an available donor, or patient declines.
  • Left Ventricular Ejection Fraction > 40%
  • No contraindications for leukapheresis (if required for retreatment)
  • Gives voluntary informed consent for retreatment

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 or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
  • 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.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification

Retreatment Exclusion Criteria

  • Pregnant or lactating women. Female study participants must have a negative serum or urine pregnancy test performed within 48 hours before infusion.
  • Uncontrolled active infection
  • Active hepatitis or hepatitis 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 on the retreatment cohort.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01747486
Other Study ID Numbers  ICMJE UPCC 03712, 816556
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Noelle Frey, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date August 2019

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