Trial record 3 of 3 for:    Pilot Study of Redirected Autologous Tcells Engineered to Contain Anti-CD19

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. (see Contacts and Locations)
Verified January 2014 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:
NCT02030834
First received: January 7, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

This is a single cohort, open-label pilot 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. Single infusion of CART-19 cells administered by i.v.

injection.


Condition Intervention Phase
Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas With no Available Potentially
Curative Treatment Options Who Have a Limited Prognosis With Currently Available Therapies.
Biological: CART-19
Phase 2

Study Type: Interventional
Study Design: 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 Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 15 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: January 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 30 patients, but will ensure that at least 8 patients each with DLBCL, MCL and FL are included.

    1. CD19+ lymphoma

      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 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.

    2. Age ≥18 years
    3. Expected survival > 12 weeks
    4. Creatinine < 1.6 mg/dL
    5. ALT/AST < 3x upper limit of normal
    6. Bilirubin <2.0 mg/dL, unless subject has Gilbert's Syndrome (<3.0 mg/dL)
    7. Any relapse after prior autologous SCT will make patient eligible regardless of other prior therapy.
    8. 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 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
    9. Measurable or assessable disease according to the "Revised Response Criteria for Malignant Lymphoma" (Cheson et al., J. Clin. Onc., 1999)105. Patients in complete remission with no evidence of disease are not eligible.
    10. Performance status (ECOG) 0 or 1.
    11. Written informed consent is given.
    12. Successful T cell test expansion (first 10 subjects

Exclusion Criteria:

  • 1. 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.

    2. Uncontrolled active infection. 3. Active hepatitis B or hepatitis C infection. 4. Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.

    5. Any uncontrolled active medical disorder that would preclude participation as outlined.

    6. HIV infection. 7. 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 8. Patients in complete remission with no assessable disease.

  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: 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
Abramson Cancer Center of the University of Pennsylvania
Investigators
Principal Investigator: Stephen Schuster, 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: NCT02030834     History of Changes
Other Study ID Numbers: UPCC 13413
Study First Received: January 7, 2014
Last Updated: January 7, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 16, 2014