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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

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ClinicalTrials.gov Identifier: NCT02030834
Recruitment Status : Completed
First Posted : January 9, 2014
Results First Posted : October 5, 2020
Last Update Posted : June 22, 2023
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Non-Hodgkins Lymphoma (NHL) Patients, With CD19+B Cell Lymphomas Biological: CART-19 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 participants
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
Actual Study Start Date : February 5, 2014
Actual Primary Completion Date : September 16, 2019
Actual Study Completion Date : September 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
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).


Outcome Measures
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Primary Outcome Measures :
  1. Number of Subjects With an Overall Response (i.e. Either Complete Response or Partial Response) Evaluated at Three Months Post Infusion. [ Time Frame: 3 months ]
    Responders will include those patients achieving complete response (CR), complete response unconfirmed (CRu) and partial response (PR) using anatomic imaging such as CT or MRI to assess tumor volume or, in the event of bone marrow involvement, morphologic and immunohistochemical confirmation that the bone marrow infiltrate has been cleared.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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
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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


Locations
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United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Stephen Schuster, MD Abramson Cancer Center at Penn Medicine
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:
Study Protocol and Statistical Analysis Plan  [PDF] August 7, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02030834    
Other Study ID Numbers: UPCC 13413, 818607
First Posted: January 9, 2014    Key Record Dates
Results First Posted: October 5, 2020
Last Update Posted: June 22, 2023
Last Verified: October 2020
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases