Clinical Trial of Autologous B7-H3 CAR T Cells in Reoccurent Platinum-resistant Ovarian Tumors

Eligibility Criteria

• 1. Disease: Histologically or cytologically confirmed diagnosis of ovarian cancer including serous, endometrioid, clear cell, mucinous, mixed epithelial, or undifferentiated. The study does not include pure sarcoma, stromal, or germ-cell tumors. Tumors that are substantially high-grade carcinoma and have focal elements of lower grade tumors or sarcomatous elements (e.g., carcinosarcoma) are eligible.
• 2. Have measurable disease. Measurable disease is defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be ≥10 mm when measured by CT, MRI, or caliper measurement at clinical examination or ≥20 mm when measured by chest x-ray. Lymph nodes must be ≥15 mm in short axis when measured by CT or MRI.
• 3. B7-H3 positive expression on malignant cells is NOT required but archival tissue must be available, or the subject must be willing to undergo tissue biopsy for expression analysis.
• 4. Age: ≥ 18 years of age
• 5. Prior Therapies: Subjects must have had at least 1 prior platinum-based chemotherapeutic regimen for the management of ovarian carcinoma.
• 6. Performance Status: ECOG status of 2 or better (or Karnofsky Performance Status score of ≥60%) (See Section 11.1)
• 7. Life expectancy at least 3 months, in the investigator's clinical judgement.
• 8. Adequate bone marrow and major organ function.
• * Hgb ≥ 10 g/dL
• * ANC ≥ 1500/uL
• * Platelet count ≥ 100,000/uL
• * Absolute lymphocyte count ≥150/uL
• * Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
• * Serum ALT and AST ≤ 5x ULN (Grade 2)
• * Total bilirubin ≤ 1.5x ULN (subjects with Gilbert's syndrome allowed if direct bilirubin within normal limits)
• * PT or PTT ≤ 1.25 X ULN (not receiving therapeutic anticoagulation)
• * Cardiac ejection fraction ≥ 45%
• * No evidence of physiologically significant pericardial effusion
• * No clinically significant ECG findings
• * Baseline oxygen saturation \> 92% on room air
• 9. Pregnancy: Females of childbearing potential (defined as women ≤50 years of age, or \>50 years of age with a history of amenorrhea for ≤12 months prior to study entry) must have a negative blood or urine pregnancy test.
• 10. Consent: Must be able to understand and be willing to personally sign the written IRB approved informed consent document.
• * 1. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• 2. Requirement for systemic corticosteroid therapy at doses higher than physiologic maintenance dosing (must be \< 5 mg/day of prednisone (or equivalent doses of other corticosteroids). Topical, inhaled or ocular steroids are allowed.
• 3. Presence of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess.
• 4. Malignant tumors other than the target tumor within 2 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 2 years prior to enrollment; or adequately treated non-melanoma skin cancers with no evidence of disease.
• 5. Have any of the following heart conditions:
• * Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
• * Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
• * History of severe nonischemic cardiomyopathy. 6. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.
• 7. Ongoing HIV, HBV, or HCV infection. History of HBV or HCV is permitted if viral load is undetectable by qPCR and/or nucleic acid testing.
• 8. Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is \>4 weeks beyond completion of cranial irradiation and \>3 weeks off of corticosteroid therapy at the time of study intervention.
• 9. Known sensitivities to any of the agents used in this study or their reagents including steroids, tocilizumab, DSMO, cyclophosphamide, fludarabine, etc.
• 10. Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures).
• 11. Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.