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Trial record 18 of 35 for:    "Ovarian Epithelial Cancer" | "Micronutrients"

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

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ClinicalTrials.gov Identifier: NCT03585764
Recruitment Status : Recruiting
First Posted : July 13, 2018
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
University of Pennsylvania

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

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Carcinoma Drug: MOv19-BBz CAR T cells Device: Alpha Folate Receptor expression test Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 19, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2035


Arm Intervention/treatment
Experimental: Cohort 1: MOv19-BBz CAR T cells without chemo
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.
Drug: MOv19-BBz CAR T cells
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.

Device: Alpha Folate Receptor expression test
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.

Experimental: Cohort 2: MOv19-BBz CAR T cells after chemo
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.
Drug: MOv19-BBz CAR T cells
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.

Device: Alpha Folate Receptor expression test
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.

Experimental: Cohort 3: MOv19-BBz CAR T cells after chemo
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.
Drug: MOv19-BBz CAR T cells
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.

Device: Alpha Folate Receptor expression test
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.

Experimental: Cohort-1: without chemo;only if dose de-escalation required
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.
Drug: MOv19-BBz CAR T cells
intraperitoneally administered lentiviral transduced MOv19-BBz CAR T cells with or without cyclophosphamide + fludarabine as lymphodepleting chemotherapy.

Device: Alpha Folate Receptor expression test
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 Measures :
  1. 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 Measures :
  1. Tumor response rates measured according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria [ Time Frame: Day 28, Month 3, Month 6 ]
  2. Progression-free survival (PFS) [ Time Frame: 5 years ]
  3. Overall response rates (ORR) [ Time Frame: 5 years ]
  4. Overall survival (OS) [ Time Frame: 15 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

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): NCT03585764


Contacts
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Contact: Payal D Shah, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
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United States, Pennsylvania
University of Pennsylvania Health System Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Payal D Shah, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Sponsors and Collaborators
University of Pennsylvania
Investigators
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Principal Investigator: Payal D Shah, MD University of Pennsylvania

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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT03585764     History of Changes
Other Study ID Numbers: 830111 (UPCC-03818)
First Posted: July 13, 2018    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

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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
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
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Micronutrients
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Cyclophosphamide
Fludarabine
Folic Acid
Vitamin B Complex
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents