Clinical Trials /

MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian Cancer

NCT03585764

Description:

Phase I study to establish safety and feasibility of intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy

Related Conditions:
  • Fallopian Tube Carcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian Cancer
  • Official Title: Phase I Clinical Trial of Adoptive Transfer of Autologous Folate Receptor - Alpha Redirected T Cells for Recurrent High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Clinical Trial IDs

  • ORG STUDY ID: 830111 (UPCC-03818)
  • NCT ID: NCT03585764

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
MOv19-BBz CAR T cellsCohort 1: MOv19-BBz CAR T cells without chemo

Purpose

Phase I study to establish safety and feasibility of intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy

Detailed Description

      This is a Phase I study evaluating the safety and feasibility of intraperitoneally
      administered lentiviral transduced MOv19-BBz CAR T cells in 4 cohorts with or without
      cyclophosphamide + fludarabine in a 3+3 dose escalation design.

      The DLT observation period is 28 days post CAR T cell infusion. The Maximum Tolerated Dose
      (MTD) is defined as the dose at which 0 or 1 DLT occurs in 6 evaluable subjects tested within
      the dose range of this study.

      Cohort 1: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced
      MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy.

      Cohort 2: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced
      MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting
      chemotherapy with cyclophosphamide + fludarabine.

      Cohort 3: (n=3 to 6 subjects): Single infusion of 1-3x108 lentivirally transduced MOv19-BBz
      CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with
      cyclophosphamide + fludarabine.

      Cohort -1: (n= 3 to 6 subjects): Single Infusion of 1-3x106 /m2 lentivirally transduced
      MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy. Up to 6 subjects will be
      infused in Cohort -1 with ≤ 1 DLT/6 subjects to establish the MTD.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: MOv19-BBz CAR T cells without chemoExperimentalCohort 1: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy.
  • MOv19-BBz CAR T cells
Cohort 2: MOv19-BBz CAR T cells after chemoExperimentalCohort 2: (n= 3 to 6 subjects): Single infusion of 1-3x107 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine.
  • MOv19-BBz CAR T cells
Cohort 3: MOv19-BBz CAR T cells after chemoExperimentalCohort 3: (n=3 to 6 subjects): Single infusion of 1-3x108 lentivirally transduced MOv19-BBz CAR T cells on day 0 beginning 3 days (+/- 1 day) after lymphodepleting chemotherapy with cyclophosphamide + fludarabine.
  • MOv19-BBz CAR T cells
Cohort-1: without chemo;only if dose de-escalation requiredExperimentalCohort -1: (n= 3 to 6 subjects): Single Infusion of 1-3x106 /m2 lentivirally transduced MOv19-BBz CAR T cells on day 0 without lymphodepleting chemotherapy. Up to 6 subjects will be infused in Cohort -1 with ≤ 1 DLT/6 subjects to establish the MTD.
  • MOv19-BBz CAR T cells

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed persistent or recurrent stage II to IV high grade serous
             epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Disease can be
             platinum-sensitive or platinum-resistant.

          2. Failure of at least two prior chemotherapy regimens for advanced stage disease. Prior
             therapies against PD-1 or PDL-1 are permissible.

          3. Confirmation of tumor aFR expression (≥70% of tumor cells with ≥2+ aFR staining).

          4. Subjects must have measureable disease as defined by RECIST 1.1 criteria.

          5. Patients with asymptomatic CNS metastases that have been treated and are off steroids
             are allowed. They must meet the following at the time of eligibility confirmation by
             investigator:

               1. No concurrent treatment for the CNS disease

               2. No progression of CNS metastasis on brain MRI at screening

               3. No evidence of leptomeningeal disease or cord compression

          6. Patients ≥ 18 years of age.

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          8. Satisfactory organ and bone marrow function as defined by the following:

             i. Absolute neutrophil count ≥ 1,000/μl ii. Platelets ≥75,000/μl iii. Hemoglobin ≥ 9
             g/dL iv. Total bilirubin ≤ 2.0x the institutional normal upper limit unless secondary
             to bile duct obstruction by tumor v. Creatinine ≤ 1.5x the institutional normal upper
             limit vi. Albumin ≥2 vii. Serum alanine aminotransferase (ALT) or aspartate
             aminotransferase (AST) ≤ 5x the institutional normal upper limit viii. Cardiac
             ejection fraction of ≥40% as measured by resting echocardiogram.

          9. Blood coagulation parameters: PT such that international normalized ratio (INR) is ≤
             1.5 and a PTT ≤ 1.2 time the upper limit of normal unless the patient is
             therapeutically anti-coagulated for history of cancer-related thrombosis and has
             stable coagulation parameters.

         10. Provides written informed consent.

         11. Subjects of reproductive potential must agree to use acceptable birth control methods,
             as described in protocol Section 4.3.

        Exclusion Criteria:

          1. High grade serous ovarian, fallopian, or primary peritoneal cancer that is platinum
             refractory, defined as disease that has clinical or radiographic progression on
             platinum-based chemotherapy, as per the discretion of the treating physician.

          2. Patients with symptomatic CNS metastases are excluded.

          3. Participation in a therapeutic investigational study within 4 weeks prior to
             eligibility confirmation by investigator, or anticipated treatment with another
             investigational product while on study. This refers to non-commercially approved
             investigational drugs different than those used in this protocol.

          4. Active invasive cancer other than ovarian cancers. Patients with active non-invasive
             cancers (such as non-melanoma skin cancer, superficial cervical and bladder cancer)
             are not excluded.

          5. HIV infection

          6. Hepatitis B or hepatitis C infection

          7. Active autoimmune disease (including but not limited to: systemic lupus erythematosus,
             Sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory
             bowel disease, etc.) requiring immunosuppressive therapy within 4 weeks prior to
             eligibility confirmation by investigator, with the exception of thyroid replacement.

          8. Patients with active and uncontrolled infection.

          9. Planned concurrent treatment with systemic high dose corticosteroids. Patients may be
             on a stable low dose of steroids (<10mg equivalent of prednisone). Corticosteroids
             treatment as anti-emetic prophylaxis on the day of lymphodepleting chemotherapy
             administration is allowed per institutional guidance.

         10. Patients requiring supplemental oxygen therapy.

         11. Prior therapy with lentiviral gene modified cells.

         12. History of allergy or hypersensitivity to study product excipients (human serum
             albumin, DMSO, and Dextran 40)

         13. Any ascites requiring therapeutic drainage within 4 weeks prior to eligibility
             confirmation by investigator.

         14. Pregnant or breastfeeding women.

         15. Presence of any other condition that may increase the risk associated with study
             participation or may interfere with the interpretation of study results, and, in the
             opinion of the investigator, would make the patient inappropriate for entry into the
             study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time Frame:15 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
Time Frame:Day 28, Month 3, Month 6
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Overall response rates (ORR)
Time Frame:5 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:15 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

August 5, 2019