Cellular Adoptive Immunotherapy in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer

Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Advanced Ovarian Cancer

RATIONALE: Biological therapies, such as cellular adoptive immunotherapy, stimulate the immune system in different ways and stop tumor cells from growing.

PURPOSE: This phase I trial is studying the side effects and best dose of cellular adoptive immunotherapy in treating patients with stage III or stage IV ovarian cancer or primary peritoneal cancer.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Peritoneal Cavity Cancer
• Intervention / Treatment: Biological: therapeutic autologous lymphocytes

Detailed Description

OBJECTIVES:

Primary

• Determine the safety and toxicity of autologous CD4-positive antigen-specific T cells in patients with stage III or IV ovarian epithelial cancer or primary peritoneal cavity cancer.
• Determine the duration of in vivo persistence of this drug in these patients.

Secondary

• Determine the antitumor effect of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis for collection of T cells. Responder T cells are stimulated in vitro with autologous peripheral blood mononuclear cell-derived dendritic cells pulsed with NY-ESO-1 immunogenic peptides. Patients receive autologous CD4-positive antigen-specific T cells IV over 30 minutes.

Cohorts of 3-6 patients receive escalating doses of autologous CD4-positive antigen-specific T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4, 8, and 12 weeks and then periodically thereafter for survival.

PROJECTED ACCRUAL: A total of 9-18 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV ovarian epithelial cancer or primary peritoneal cavity cancer meeting 1 of the following criteria:

  • Progressive* or persistent* disease during or after primary chemotherapy
  • Recurrent disease < 6 months after completion of primary therapy that had resulted in a complete response
  • Persistent* or recurrent disease after second-line or additional therapies NOTE: *Progression or persistence can be based on serological (CA 125 > 100 U/mL OR 2 times baseline), radiographic (measurable or evaluable disease), or second-look surgical findings
• Tumor expressing NY-ESO-1 determined by IHC or RT-PCR
• HLA type expressing DPB*0401, DPB1*0201, DRB1*07
• No CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 to 75

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 16 weeks

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Creatinine ≤ 2.0 mg/dL

Cardiovascular

• No congestive heart failure*
• No clinically significant hypotension*
• No symptoms of coronary artery disease*
• No cardiac arrhythmias on EKG requiring drug therapy*
• No history of cardiovascular disease*
• No other significant cardiovascular abnormalities* NOTE: *Patients with any of the above undergo a stress test and/or echocardiography before being determined ineligible for study participation

Pulmonary

• FEV_1 ≥ 60% of predicted*
• DLCO ≥ 55%* NOTE: *Patients with clinically significant pulmonary dysfunction only

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No active infection
• No oral temperature > 38.2°C within the past 72 hours
• No systemic infection requiring chronic maintenance or suppressive therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy (e.g., interleukins, interferons, vaccines, intravenous immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or lymphokine-activated killer cell therapy)

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior standard or experimental chemotherapy

Endocrine therapy

• No concurrent systemic corticosteroids except for treatment-related toxicity

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 3 weeks since prior immunosuppressive therapy
• More than 3 weeks since prior investigational drugs and recovered
• No other concurrent investigational agents
• No concurrent pentoxifylline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and toxicity
Duration of in vivo persistence
Antitumor effects

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Study Completion (ACTUAL): March 1, 2010

Study Registration Dates

• First Submitted: January 7, 2005
• First Submitted That Met QC Criteria: January 7, 2005
• First Posted (ESTIMATE): January 10, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): May 7, 2010
• Last Update Submitted That Met QC Criteria: May 5, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; peritoneal cavity cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: 1942.00; FHCRC-1942.00; CDR0000402870 (REGISTRY: PDQ)