Clinical Trials /

Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells in Patients With Refractory or Relapsed Hodgkin Lymphoma

NCT02624258

Description:

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 TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Terminated

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells in Patients With Refractory or Relapsed Hodgkin Lymphoma
  • Official Title: Pilot Study of Non-Viral, RNA-Redirected Autologous T Cells Engineered to Contain Anti-CD19 Linked to TCR and 4-1BB Signaling Domains in Patients With Refractory or Relapsed Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 14BT055, 821157
  • NCT ID: NCT02624258

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
CD19 RNA redirected autologous T-cells (RNA CART19 cells)RNA CART19 cells

Purpose

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 TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "RNA CART19") in Hodgkin Lymphoma (HL) patients. Subjects will be treated with IV administration of RNA anti-CD19 CAR T cells for a total of six doses over 3 weeks.

Detailed Description

      The study will enroll 10 evaluable patients. Evaluable patients are those who have received
      at least 1 of the 6 RNA CART19 doses at the protocol-specified level. Important safety data
      can be collected even if a patient receives only one RNA CART19 dose. Subjects (n = 10) will
      receive up to six IV doses of 8x105-1.5x106 RNA CART19 cells/kg/dose for subjects<80kg and
      1x108 RNA CART19 cells/dose (±20%) for subjects ≥80kg.

      The RNA CART19 doses and mid-treatment single dose cyclophosphamide will be administered on
      Mondays, Wednesdays or Fridays. Dosing can be initiated on any of those days. Subjects will
      be infused in a staggered fashion at two week intervals; that is, the next subject cannot be
      infused prior to two weeks since the last infusion of the previous subject.
    

Trial Arms

NameTypeDescriptionInterventions
RNA CART19 cellsExperimentalCD19 RNA redirected autologous T-cells (RNA CART19 cells)
  • CD19 RNA redirected autologous T-cells (RNA CART19 cells)

Eligibility Criteria

        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.

               -  HL with biopsy-proven relapse or refractory disease who are unresponsive to or
                  intolerant of at least one line of standard salvage therapy;

               -  Patients must have evaluable disease by radiologic imaging (FDG PET-CT or FDG
                  PET-MRI) within 42 day of enrollment; evaluable includes both assessable and/or
                  measurable disease

          -  Age 18 to 24 years. Patients ages 22-24 will only be enrolled if they are currently
             being treated at CHOP or another pediatric facility/oncologist.

          -  Expected survival > 12 weeks at time of screening

          -  Adequate organ function defined as:

          -  Renal function defined as:

               -  Creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m2 OR

               -  Serum creatinine: < 1.7mg/dL (male subjects) or < 1.4mg/dL (female subjects)

          -  ALT < 5 times the ULN for age

          -  Total Bilirubin < 2.0 mg/dl

          -  Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse
             oxygenation > 94% on room air

          -  Patients with relapsed disease after prior allogeneic SCT (myeloablative or
             non-myeloablative) will be eligible if they meet all other inclusion criteria and

          -  Have no active GVHD and require no immunosuppression

          -  Are more than 6 months from transplant 6) Karnofsky performance status ≥ 50 at
             screening

          -  Left Ventricular Shortening Fraction (LVSF) > 28% confirmed by echocardiogram, or Left
             Ventricular Ejection Fraction (LVEF) > 45% confirmed by echocardiogram or MUGA

          -  Signed written informed consent must be obtained prior to any study procedures

          -  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 pregnancy test will be performed within 48 hours
             before the 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 known 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 by radiologic imaging of disease.

          -  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

          -  Unstable angina and/or myocardial infarction within 6 months prior to screening.
      
Maximum Eligible Age:24 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events, defined as NCI CTCAE V4 > Grade 3
Time Frame:Month 4 post-CART19 Infusion
Safety Issue:
Description:Occurrence of study related adverse events, defined as NCI CTCAE V4 > grade 3 signs/symptoms, laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the first cyclophosphamide infusion until Month 4.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

September 10, 2019