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

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02030834
Recruitment Status : Active, not recruiting
First Posted : January 9, 2014
Last Update Posted : March 21, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

January 7, 2014
January 9, 2014
March 21, 2018
February 5, 2014
September 2018   (Final data collection date for primary outcome measure)
Number of Adverse Events [ Time Frame: 15 months ]
Same as current
Complete list of historical versions of study NCT02030834 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
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
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
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.
Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas
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 A
    murine CART19
    Intervention: Biological: CART-19
  • Experimental: Cohort B
    T cell/histiocyte-rich Diffuse Large B Cell Lymphoma (DLBCL) treated with murine CART19
    Intervention: Biological: CART-19
  • Experimental: Cohort C
    Diffuse Large B Cell Lymphoma (DLBCL) treated with humanized CART19
    Intervention: Biological: CART-19
Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak Ö, Brogdon JL, Pruteanu-Malinici I, Bhoj V, Landsburg D, Wasik M, Levine BL, Lacey SF, Melenhorst JJ, Porter DL, June CH. Chimeric Antigen Receptor T Cells in Refractory B-Cell Lymphomas. N Engl J Med. 2017 Dec 28;377(26):2545-2554. doi: 10.1056/NEJMoa1708566. Epub 2017 Dec 10.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
63
55
August 2019
September 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02030834
UPCC 13413, 818607
Yes
Not Provided
Not Provided
University of Pennsylvania
University of Pennsylvania
Not Provided
Principal Investigator: Stephen Schuster, MD Abramson Cancer Center of the University of Pennsylvania
University of Pennsylvania
March 2018

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