ClinicalTrials.gov processed this data on March 28, 2024Link to the current ClinicalTrials.gov record.https://clinicaltrials.gov/ct2/show/NCT000059411477.00FHCRC-1477.00NCI-G00-1784CDR0000067816NCT00005941Peripheral Stem Cell Transplant, White Blood Cell Infusions, Chemotherapy, and Radiation Therapy in Treating Patients With Recurrent Metastatic Cervical or Vaginal CancerPhase 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 TherapyFred Hutchinson Cancer CenterOtherNational Cancer Institute (NCI)NIH
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.
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.
CompletedNovember 1999June 2005June 2005Phase 2InterventionalNoTreatmentNone (Open Label)Partial or complete responseToxicityEngraftment and donor chimerismHPV-E6 and E7-specific T cell responsesCervical CancerVaginal CancerBiologicaltherapeutic allogeneic lymphocytesDrugcyclosporineDrugfludarabine phosphateDrugmycophenolate mofetilProcedureperipheral blood stem cell transplantationRadiationradiation therapy
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
FemaleN/A64 YearsNoRichard Nash, MDStudy ChairFred Hutchinson Cancer CenterFred Hutchinson Cancer Research CenterSeattleWashington98109-1024United StatesUnited StatesMarch 2010July 5, 2000January 26, 2003January 27, 2003March 31, 2010March 31, 2010April 2, 2010stage III cervical cancerrecurrent cervical cancerstage IVB cervical cancerstage IVA cervical cancerstage III vaginal cancerstage IVA vaginal cancerstage IVB vaginal cancerrecurrent vaginal cancerUterine Cervical NeoplasmsVaginal NeoplasmsCyclosporineMycophenolic AcidFludarabineFludarabine phosphateCyclosporins