Peripheral Stem Cell Transplant, White Blood Cell Infusions, Chemotherapy, and Radiation Therapy in Treating Patients With Recurrent Metastatic Cervical or Vaginal Cancer
RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well donor peripheral stem cell transplant plus chemotherapy and total-body irradiation followed by donor white blood cell infusion work in treating patients with recurrent metastatic or locally advanced cancer of the cervix or vagina that is associated with human papillomavirus.
Biological: therapeutic allogeneic lymphocytes
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Pilot Trial of Non-Myeloablative Allogeneic Peripheral Blood Stem Cell (PBSC) Transplantation Using Fludarabine, Low Dose TBI and Post-Transplant Cyclosporine and Mycophenolate Mofetil Followed by Donor Lymphocyte Infusion for Therapy of Advanced or Metastatic Human Papilloma Virus (HPV) - Associated Cervical Carcinoma Refractory to Standard Therapy|
- Partial or complete response [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Engraftment and donor chimerism [ Designated as safety issue: No ]
- HPV-E6 and E7-specific T cell responses [ Designated as safety issue: No ]
|Study Start Date:||November 1999|
|Study Completion Date:||June 2005|
|Primary Completion Date:||June 2005 (Final data collection date for primary outcome measure)|
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005941
|United States, Washington|
|Fred Hutchinson Cancer Research Center|
|Seattle, Washington, United States, 98109-1024|
|Study Chair:||Richard Nash, MD||Fred Hutchinson Cancer Research Center|