Autologous T-Cells Combined With Autologous OC-DC Vaccine in Ovarian Cancer

NCT01312376 | Terminated Phase 1 DMC

• 2 other identifiers: UPCC 26810, R01 FD 003520FDA 00PD
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase-I clinical trial to determine the feasibility and safety of Cyclophosphamide/Fludarabine Lymphodepletion and an immunomodulatory combination of Interferon-alpha Bevacizumab and Aspirin followed by adoptive transfer of vaccine-primed ex vivo CD3/CD28-costimulated peripheral blood autologous T cells and vaccination with whole tumor vaccine administered intradermally in combination with Bevacizumab in patients with recurrent ovarian cancer fallopian tube or primary peritoneal cancer. (Funding Source - FDA OOPD)

Conditions

Ovarian Carcinoma; Fallopian Tube Cancer; Primary Peritoneal Cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Dose limiting toxicity is defined as the occurrence of treatment-related adverse events.

  5 Years

Secondary Outcomes (1)

• Tumor response

  5 years

Interventions

OC-DC vaccine BIOLOGICAL

All subjects will receive a dose of 5-10 million cells of OC-DC intradermally

Bevacizumab DRUG

Patients will start receiving Bevacizumab at 15 mg/kg starting Day 30 and every 4 weeks thereafter until end of study.

cyclophosphamide 300 mg/m2/d for 3 days DRUG

All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous cyclophosphamide for 300 mg/m2/d for 3 days.

fludarabine 30 mg/m2/d for 3 days DRUG

All subjects will receive a single course of outpatient lympho-depleting chemotherapy with intravenous fludarabine 30 mg/m2/d for 3 days

ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T cells DRUG

All subjects will receive a single intravenous infusion of ex vivo CD3/CD28-costimulated vaccine-primed peripheral blood autologous T-cells at the starting dose of 10-15 x 109 (10-15 billion) T-cells with escalating doses in cohort 2 and 3.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who have received at least one vaccine under protocol UPCC-19809 or UPCC-29810.
• ECOG performance status 0 or 1.
• Subject has sufficient vaccine (2 vaccine doses are sufficient)
• Must be at least 4 weeks post-operative
• Blood coagulation parameters: PT such that international normalized ratio (INR) is less than1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT less than1.2 times the upper limit of normal.
• Subject must be 18 years of age or older.
• Life expectancy of greater than 4 months.
• Normal organ and bone marrow function as defined by: Absolute neutrophil count greater than 1,000/microliter, Platelets greater than 100,000/microliter, Hematocrit greater than 30%, AST (SGOT)/ALT(SGPT) less than 2.5 X institutional upper limit of normal, Bilirubin less than 2.0 mg/dL unless secondary to bile duct blockage by tumor, and Creatinine less than 1.8 mg/dL

You may not qualify if:

• Subjects who require or are likely to require more than a two-week course of corticosteroids for intercurrent illness. Subjects must complete therapy prior to enrollment. Topical corticosteroids should be stopped at least 2 weeks prior to enrollment and systemic corticosteroids should be stopped at least 4 weeks prior to enrollment.
• Subjects with any acute infection that requires specific therapy. Acute therapy must have been completed at least seven days prior to study enrollment
• Subjects with any underlying conditions, which would contraindicate therapy with, study treatment (or allergies to reagents used in this study).
• Subjects with prior history or symptoms suggestive of partial or complete bowel obstruction.
• Subjects receiving class III antiarrythmic medications.
• Subjects receiving medications that might affect immune function. Additionally, H2 blockers are excluded, as are all antihistamines five days before and five days after each injection of study drug. NOTE: The following are exceptions: Proton pump Inhibitors (PPIs), NSAIDS including COX-2 inhibitors, acetaminophen.
• Subjects who are allergic to Aspirin are excluded
• Development of clinically significant co morbid disease that would contraindicate study therapy or confuse interpretation of study results.
• Subjects with a History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess.
• Subjects with evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Bobisse S, Bianchi V, Tanyi JL, Sarivalasis A, Missiaglia E, Petremand R, Benedetti F, Torigian DA, Genolet R, Barras D, Michel A, Mastroyannis SA, Zsiros E, Dangaj Laniti D, Tsourti Z, Stevenson BJ, Iseli C, Levine BL, Speiser DE, Gfeller D, Bassani-Sternberg M, Powell DJ Jr, June CH, Dafni U, Kandalaft LE, Harari A, Coukos G. A phase 1 trial of adoptive transfer of vaccine-primed autologous circulating T cells in ovarian cancer. Nat Cancer. 2023 Oct;4(10):1410-1417. doi: 10.1038/s43018-023-00623-x. Epub 2023 Sep 21.

  PMID: 37735588 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Bevacizumab; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Janos Tanyi, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2011
• First Posted: March 10, 2011
• Study Start: March 1, 2011
• Primary Completion: October 1, 2015
• Study Completion: January 1, 2019
• Last Updated: April 24, 2020

Record last verified: 2020-04

Locations

US (1)