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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 1

Conditions: Peritoneal Cavity Cancer; Ovarian Cancer

Treatments: Biological: therapeutic autologous lymphocytes

Study type: Interventional

Funder types: Other

Identifiers

NCT00101257

CDR0000402870 (Registry Identifier)

1942.00

FHCRC-1942.00

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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