We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas

This study is currently recruiting participants.
Verified June 2017 by University of Pennsylvania
Sponsor:
ClinicalTrials.gov Identifier:
NCT02030834
First Posted: January 9, 2014
Last Update Posted: July 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Pennsylvania
  Purpose
Phase IIa study to estimate the efficacy of a single infusion of autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as CART-19 or CTL019 cells) in non-Hodgkins Lymphoma (NHL) patients. The duration of active protocol intervention is approximately 24 months from screening visit. The protocol will require approximately 48 months to complete.

Condition Intervention Phase
Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas Biological: CART-19 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase IIa Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Attached to TCRz and 4-Signaling Domains in Patients With Chemotherapy Relapsed or Refractory CD19+ Lymphomas

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 15 months ]

Estimated Enrollment: 57
Actual Study Start Date: February 5, 2014
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A
murine CART19
Biological: CART-19
Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells).
Experimental: Cohort B
T cell/histiocyte-rich Diffuse Large B Cell Lymphoma (DLBCL) treated with murine CART19
Biological: CART-19
Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells).
Experimental: Cohort C
Diffuse Large B Cell Lymphoma (DLBCL) treated with humanized CART19
Biological: CART-19
Single infusion of CART-19 cells administered by i.v. injection (total dose of 1 - 5 x108 CART-19 cells, calculated as a range of 2-50% transduced cells in total cells).

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Male or female subjects with CD19+ B cell lymphomas with no available curative treatment options (such as autologous or allogeneic SCT) who have a limited prognosis (several months to <2 year survival) with currently available therapies will be enrolled. The study will enroll 51 evaluable subjects as follows:
  • CD19+ Lymphoma

Cohort A Subjects:

a. Follicular lymphoma, previously identified as CD19+ i. At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy) ii. Patients who progress within 2 years after second or higher line of therapy will be eligible. For instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible. Patients may have progression, stable disease or responding disease at the time of enrollment.

iii. Patients with a history of large cell transformation are eligible. b. Mantle cell lymphoma, previously identified as CD19+ i. Beyond 1st CR with relapsed disease, progressive disease during first line rituximab-chemotherapy combination, or persistent disease after first line rituximab-chemotherapy combination and not eligible or appropriate for conventional allogeneic or autologous SCT.

ii. Relapsed after prior autologous SCT. c. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.

Cohort B Subjects:

a. Diffuse large B cell lymphoma, previously identified as CD19+ CD19 i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.

v. Patients with T cell/histiocyte-rich disease as confirmed by surgical pathology report

Cohort C Subjects:

a. Diffuse large B cell lymphoma, previously identified as CD19+ i. Residual disease after primary therapy and not eligible for autologous SCT ii. Relapsed or persistent disease after prior autologous SCT iii. Beyond 1st CR with relapsed or persistent disease and not eligible or appropriate for conventional allogeneic or autologous SCT iv. Patients with an antecedent history of follicular lymphoma or CLL/SLL are eligible.

  • Age ≥18 years
  • Creatinine < 1.6 mg/dL
  • ALT/AST < 3x upper limit of normal
  • Bilirubin <2.0 mg/dL, unless subject has Gilbert's Syndrome (<3.0 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 non-myeloablative) 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
  • Measurable or assessable disease according to the "Revised Response Criteria for Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 1999)108. Patients in complete remission with no evidence of disease are not eligible.
  • Performance status (ECOG) 0 or 1.
  • Left Ventricle Ejection Fraction (LVEF) > 40% confirmed by ECHO/MUGA
  • Written informed consent is given. Successful T cell test expansion (first 10 subjects).

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 pregnancy test at enrollment. A urine pregnancy test will be 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. For additional details regarding use of steroids
  • Any uncontrolled active medical disorder that would preclude participation as outlined.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
  • HIV infection.
  • Patients with active CNS involvement by malignancy. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was >4 weeks before enrollment
  • Patients in complete remission with no assessable disease.
  • Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02030834


Contacts
Contact: Stephen Schuster, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Stephen Schuster, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Stephen Schuster, MD         
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Stephen Schuster, MD Abramson Cancer Center of the University of Pennsylvania
  More Information

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02030834     History of Changes
Other Study ID Numbers: UPCC 13413
First Submitted: January 7, 2014
First Posted: January 9, 2014
Last Update Posted: July 2, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases