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
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
830111 (UPCC-03818)
- NCT ID:
NCT03585764
Conditions
- Ovarian Cancer
- Fallopian Tube Cancer
- Primary Peritoneal Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
MOv19-BBz CAR T cells | | Cohort 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
Name | Type | Description | Interventions |
---|
Cohort 1: MOv19-BBz CAR T cells without chemo | Experimental | 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: MOv19-BBz CAR T cells after chemo | Experimental | 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: MOv19-BBz CAR T cells after chemo | Experimental | 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: without chemo;only if dose de-escalation required | Experimental | 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. | |
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
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.
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
February 5, 2021