Peripheral Stem Cell Transplant, White Blood Cell Infusions, Chemotherapy, and Radiation Therapy in Treating Patients With Recurrent Metastatic Cervical or Vaginal Cancer

OBJECTIVES:

Primary

• Determine the partial or complete response in patients with recurrent metastatic or locally advanced human papillomavirus (HPV)-associated cervical or vaginal carcinoma treated with a nonmyeloablative regimen comprising fludarabine and low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation, cyclosporine, mycophenolate mofetil, and donor lymphocyte infusion.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine whether this regimen induces engraftment and donor chimerism in these patients.
• Determine the HPV-E6 and HPV-E7 specific T-cell responses in selected patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive conditioning therapy comprising fludarabine IV on days -4 to -2 and low-dose total body irradiation on day 0. Filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cells are infused on day 0.

Patients also receive oral cyclosporine twice daily on days -3 to 35 and then tapered until day 56. Mycophenolate mofetil is administered orally twice daily on days 0-27.

Patients with disease progression and no graft-versus-host disease on day 56 receive nonmobilized donor lymphocyte infusion (DLI) over 30 minutes on day 65. DLI may be repeated every 65 days for up to 4 doses.

Patients are followed weekly for 3 months, monthly for 6 months, every 6 months for 2 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed recurrent metastatic or locally advanced cervical or vaginal carcinoma that is not curable with surgery or radiotherapy

• Tumor is human papillomavirus positive by polymerase chain reaction
• Bidimensionally measurable disease by clinical examination or radiographic imaging
• Availability of an genotypically HLA-identical sibling donor (excluding identical twins)
• No brain metastases

PATIENT CHARACTERISTICS:

Age:

• Under 65

Performance status:

• Karnofsky 80-100%

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 2 times ULN

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• Cardiac ejection fraction at least 40%
• No history of congestive heart failure
• No poorly controlled hypertension

Pulmonary:

• No severe defects in pulmonary function
• No supplementary continuous oxygen

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study completion
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Concurrent growth factors for severe persistent or febrile neutropenia after transplantation allowed

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics