Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003553

Purpose

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, before a donor peripheral blood stem cell transplant helps stop the growth of tumor cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining tumor 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 with or without mycophenolate mofetil or methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well peripheral stem cell transplant works in treating patients with metastatic kidney cancer.

Condition	Intervention	Phase
Kidney Cancer	Biological: anti-thymocyte globulin Drug: cyclophosphamide Drug: cyclosporine Drug: fludarabine phosphate Drug: methotrexate Drug: mycophenolate mofetil	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation for Metastatic Renal Cell Carcinoma Followed by Allogeneic T-Cell Infusion as Adoptive Immunotherapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Kidney Cancer

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

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Graft vs tumor effect as measured by CT scan at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-free survival as measured by CT scan at 6 months and 1 year [ Designated as safety issue: No ]

Estimated Enrollment:	80
Study Start Date:	January 1999
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Preparative regimen 1: Experimental Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.	Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV
Preparative regimen 2 (closed to accrual as of 10/1/03): Experimental Patients receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.	Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV
Preparative regimen 3 (closed to accrual as of 10/1/03): Experimental Patients receive cyclophosphamide IV over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.	Biological: anti-thymocyte globulin Given IV Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV
GVHD regimen 1 (closed to accrual as of 10/17/00): Experimental Patients receive cyclosporine IV over 12 hours or orally beginning on day -4 and continuing for up to approximately 3 months.	Drug: cyclosporine Given IV
GVHD regimen 2 (open to accrual from 10/17/00 through 2/11/02): Experimental Patients receive cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.	Drug: cyclosporine Given IV Drug: mycophenolate mofetil Given as GVHD prophylaxis
GVHD regimen 3 (open to accrual as of 2/11/02): Experimental Patients receive cyclosporine as in regimen 1. Patients also receive methotrexate.	Drug: cyclosporine Given IV Drug: methotrexate Given as GVHD prophylaxis

Detailed Description:

OBJECTIVES:

Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with metastatic renal cell carcinoma.
Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative regimen followed by an HLA-matched allogeneic PBSCT in these patients.
Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid lineages in patients treated with this regimen.
Determine the relationship between donor-host chimerism and the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
Determine the effect of lymphocyte infusions on donor-host chimerism in this patient population.
Determine the response rate, disease-free survival, overall survival, and mortality from the procedure or tumor progression in patients treated with this regimen.

OUTLINE:

Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens prior to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3 closed to accrual as of 10/1/03.)
- Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1.
- Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.
- Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2.
PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may be repeated on days 1 and 2, if deemed necessary.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis regimens.
- Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV over 12 hours or orally beginning on day -4 and continuing for up to approximately 3 months.
- Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil.
- Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive methotrexate.
Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor lymphocyte infusions after day 100 may be given at the discretion of the attending physician.

Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then every 6 months for 2½ years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically proven metastatic renal cell carcinoma not amenable to complete surgical resection and progressive despite immunotherapy
Bidimensionally evaluable clinically or radiographically
HLA 6/6 or 5/6 matched family donor available
No CNS metastases

PATIENT CHARACTERISTICS:

Age:

18 to 80

Performance status:

ECOG 0 or 1

Life expectancy:

At least 3 months

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 4 mg/dL
Transaminases no greater than 3 times upper limit of normal

Renal:

Creatinine no greater than 2.5 mg/dL
No malignancy-associated hypercalcemia (< 2.5 mmol/L)

Cardiovascular:

Left ventricular ejection fraction greater than 40%

Pulmonary:

DLCO greater than 65% of predicted

Other:

Not pregnant
HIV negative
No major organ dysfunction that would preclude transplantation
No other malignancies except basal cell or squamous cell skin cancer
No psychiatric disorder or mental deficiency that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

At least 1 month since prior treatment for renal cell carcinoma

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003553

Locations

United States, Maryland
NIH - Warren Grant Magnuson Clinical Center	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Patient Recruitment 800-411-1222

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:

Richard W. Childs, MD

National Heart, Lung, and Blood Institute (NHLBI)

More Information

Additional Information:

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

Publications:

Childs R, Chernoff A, Contentin N, Bahceci E, Schrump D, Leitman S, Read EJ, Tisdale J, Dunbar C, Linehan WM, Young NS, Barrett AJ. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med. 2000 Sep 14;343(11):750-8.

Carvallo C, Geller N, Kurlander R, Srinivasan R, Mena O, Igarashi T, Griffith LM, Linehan WM, Childs RW. Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood. 2004 Feb 15;103(4):1560-3. Epub 2003 Oct 9.

Responsible Party:	National Heart, Lung, and Blood Institute ( Richard W. Childs )
Study ID Numbers:	CDR0000066610, NHLBI-97-H-0196
Study First Received:	November 1, 1999
Last Updated:	June 23, 2009
ClinicalTrials.gov Identifier:	NCT00003553 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IV renal cell cancer
recurrent renal cell 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
Urogenital Neoplasms
Reproductive Control Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Urologic Neoplasms

Cyclosporins
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Antifungal Agents
Therapeutic Uses
Abortifacient Agents
Mycophenolate mofetil
Methotrexate
Kidney Diseases
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Enzyme Inhibitors

ClinicalTrials.gov processed this record on November 27, 2009