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CD19 Redirected Autologous T Cells for Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT02277522
Recruitment Status : Terminated (unable to meet enrollment goal)
First Posted : October 29, 2014
Last Update Posted : November 9, 2017
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

Tracking Information
First Submitted Date  ICMJE October 27, 2014
First Posted Date  ICMJE October 29, 2014
Last Update Posted Date November 9, 2017
Study Start Date  ICMJE October 2014
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
Number of Adverse Events [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CD19 Redirected Autologous T Cells for Hodgkin Lymphoma
Official Title  ICMJE Pilot Study of Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCRζ and 4-1BB Signaling Domains in Patients With Chemotherapy Relapsed or Refractory Hodgkin Lymphoma
Brief Summary Pilot open-label study to estimate the feasibility, safety and efficacy of intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCR and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19) in Hodgkin Lymphoma (HL) patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma With no Available Curative Treatment Options Who Have a Limited Prognosis
Intervention  ICMJE Biological: RNA anti-CD19 CAR T cells
intravenously administered, RNA electroporated autologous T cells expressing CD19 chimeric antigen receptors expressing tandem TCRζ and 4-1BB (TCR /4-1BB) costimulatory domains (referred to as RNA CART19)
Study Arms  ICMJE Experimental: RNA autologous T cells (anti CD19 CAR T cells)
Intervention: Biological: RNA anti-CD19 CAR T cells
Publications * Svoboda J, Rheingold SR, Gill SI, Grupp SA, Lacey SF, Kulikovskaya I, Suhoski MM, Melenhorst JJ, Loudon B, Mato AR, Nasta SD, Landsburg DJ, Youngman MR, Levine BL, Porter DL, June CH, Schuster SJ. Nonviral RNA chimeric antigen receptor-modified T cells in patients with Hodgkin lymphoma. Blood. 2018 Sep 6;132(10):1022-1026. doi: 10.1182/blood-2018-03-837609. Epub 2018 Jun 20.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 30, 2016)
4
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2014)
16
Actual Study Completion Date  ICMJE June 27, 2017
Actual Primary Completion Date November 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female subjects with HL with no available curative treatment options (such as autologous SCT) who have a limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled.

    i. HL with biopsy-proven relapse or refractory disease who are unresponsive to or intolerant of at least one line of standard salvage therapy ii. Patients must have evaluable disease by radiologic imaging (FDG PET/CT or PET/MRI) within 42 days of enrollment; evaluable includes both assessable and/or measurable disease as defined by Cheson et al., 2007.

  • Age ≥ 18 years of age
  • 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)
  • 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
  • Performance status (ECOG) 0 or 1.
  • Left Ventricular Ejection Fraction (LVEF) ≥ 40% as confirmed by ECHO/MUGA
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air
  • Written informed consent is given.
  • Successful T cell test expansion (to be performed as part of inclusion criteria until 3 subjects meet all enrollment criteria)

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 or serum pregnancy test will be performed within 72 hours before the first RNA CART19 infusion.
  • Uncontrolled active infection.
  • Active hepatitis B or hepatitis C infection.
  • Any uncontrolled active medical disorder that would preclude participation as outlined.
  • HIV infection.
  • Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
  • 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 evidence of evaluable disease by radiologic imaging.
  • History of allergy to murine proteins.
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
  • Anti-CD20 monoclonal antibody therapy within the last 3 months, or absence of circulating B cells.
  • Class III/IV cardiovascular disability according to the New York Heart Association Classification (see Appendix 1).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02277522
Other Study ID Numbers  ICMJE UPCC 04414, 820840
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Pennsylvania
Study Sponsor  ICMJE University of Pennsylvania
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jakub Svoboda, MD Abramson Cancer Center of the University of Pennsylvania
PRS Account University of Pennsylvania
Verification Date November 2017

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