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MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Primary Purpose

Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MOv19-BBz CAR T cells
Alpha Folate Receptor expression test
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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 physician-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%.

  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 physician-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 requiring systemic immunosuppressive treatment equivalent to >/= 10mg of prednisone. Patients with autoimmune neurologic diseases (such as multiple sclerosis) will be excluded. (.
  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 physician-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 physician-investigator, would make the patient inappropriate for entry into the study.

Sites / Locations

  • University of Pennsylvania Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1: MOv19-BBz CAR T cells without chemo

Cohort 2: MOv19-BBz CAR T cells after chemo

Cohort 3: MOv19-BBz CAR T cells after chemo

Cohort-1: without chemo;only if dose de-escalation required

Arm Description

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.

Outcomes

Primary Outcome Measures

Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Secondary Outcome Measures

Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
Progression-free survival (PFS)
Overall response rates (ORR)
Overall survival (OS)

Full Information

First Posted
July 2, 2018
Last Updated
June 21, 2023
Sponsor
University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT03585764
Brief Title
MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal 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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 24, 2018 (Actual)
Primary Completion Date
October 2038 (Anticipated)
Study Completion Date
October 2038 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1: MOv19-BBz CAR T cells without chemo
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2: MOv19-BBz CAR T cells after chemo
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3: MOv19-BBz CAR T cells after chemo
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort-1: without chemo;only if dose de-escalation required
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MOv19-BBz CAR T cells
Intervention Description
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.
Intervention Type
Device
Intervention Name(s)
Alpha Folate Receptor expression test
Intervention Description
Patients will first be pre-screened for alpha folate receptor expression. The test for alpha folate receptor expression is a laboratory developed test+, developed and conducted by the Hospital of the University of Pennsylvania Pathology and Laboratory Medicine lab to determine subject eligibility. This test is not an approved FDA device and its use is investigational.
Primary Outcome Measure Information:
Title
Number of study subjects with treatment-related adverse events using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Time Frame
15 years
Secondary Outcome Measure Information:
Title
Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
Time Frame
Day 28, Month 3, Month 6
Title
Progression-free survival (PFS)
Time Frame
5 years
Title
Overall response rates (ORR)
Time Frame
5 years
Title
Overall survival (OS)
Time Frame
15 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Failure of at least two prior chemotherapy regimens for advanced stage disease. Prior therapies against PD-1 or PDL-1 are permissible. Confirmation of tumor aFR expression (≥70% of tumor cells with ≥2+ aFR staining). Subjects must have measureable disease as defined by RECIST 1.1 criteria. 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 physician-investigator: No concurrent treatment for the CNS disease No progression of CNS metastasis on brain MRI at screening No evidence of leptomeningeal disease or cord compression Patients ≥ 18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 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%. 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. Provides written informed consent. Subjects of reproductive potential must agree to use acceptable birth control methods, as described in protocol Section 4.3. Exclusion Criteria: 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. Patients with symptomatic CNS metastases are excluded. Participation in a therapeutic investigational study within 4 weeks prior to eligibility confirmation by physician-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. 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. HIV infection Hepatitis B or hepatitis C infection Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to >/= 10mg of prednisone. Patients with autoimmune neurologic diseases (such as multiple sclerosis) will be excluded. (. Patients with active and uncontrolled infection. 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. Patients requiring supplemental oxygen therapy. Prior therapy with lentiviral gene modified cells. History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40) Any ascites requiring therapeutic drainage within 4 weeks prior to eligibility confirmation by physician-investigator. Pregnant or breastfeeding women. 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 physician-investigator, would make the patient inappropriate for entry into the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Abranmson Cancent Center Clinical Trials Service, MD
Phone
855-216-0098
Email
PennCancerTrials@careboxhealth.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Payal D Shah, MD
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania Health System
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Payal D Shah, MD
Phone
855-216-0098
Email
PennCancerTrials@careboxhealth.com

12. IPD Sharing Statement

Learn more about this trial

MOv19-BBz CAR T Cells in aFR Expressing Recurrent High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

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