Trial record 1 of 1 for:    NCT01747486.
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CD19 Redirected Autologous T Cells

This study is ongoing, but not recruiting participants.
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: January 28, 2016
Last verified: January 2016
  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 ]

Enrollment: 59
Study Start Date: December 2012
Primary Completion Date: January 2016 (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
  • 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
  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

Locations
United States, Pennsylvania
Abramsonc Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
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

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: January 28, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on May 26, 2016