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.

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.

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