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

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00005941

Purpose

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.

Condition	Intervention	Phase
Cervical Cancer Vaginal Cancer	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Vaginal Cancer

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:

Partial or complete response [ Designated as safety issue: No ]

Secondary Outcome Measures:

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)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 64 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005941

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Richard Nash, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000067816, FHCRC-1477.00, NCI-G00-1784
Study First Received:	July 5, 2000
Last Updated:	July 2, 2009
ClinicalTrials.gov Identifier:	NCT00005941 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:

stage III cervical cancer
recurrent cervical cancer
stage IVB cervical cancer
stage IVA cervical cancer

stage III vaginal cancer
stage IVA vaginal cancer
stage IVB vaginal cancer
recurrent vaginal cancer

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Vaginal Diseases
Urogenital Neoplasms
Antibiotics, Antineoplastic
Cyclosporins
Genital Diseases, Female

Neoplasms by Site
Antifungal Agents
Therapeutic Uses
Mycophenolate mofetil
Dermatologic Agents
Vaginal Neoplasms
Genital Neoplasms, Female
Enzyme Inhibitors
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Fludarabine
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 09, 2009