Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003553
First received: November 1, 1999
Last updated: June 23, 2009
Last verified: June 2009
  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 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
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:


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
Experimental: Preparative 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.
Drug: cyclophosphamide
Given IV
Drug: fludarabine phosphate
Given IV
Experimental: Preparative 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.

Drug: cyclophosphamide
Given IV
Drug: fludarabine phosphate
Given IV
Experimental: Preparative 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.
Biological: anti-thymocyte globulin
Given IV
Drug: cyclophosphamide
Given IV
Drug: fludarabine phosphate
Given IV
Experimental: GVHD 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.
Drug: cyclosporine
Given IV
Experimental: GVHD 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.
Drug: cyclosporine
Given IV
Drug: mycophenolate mofetil
Given as GVHD prophylaxis
Experimental: GVHD regimen 3 (open to accrual as of 2/11/02)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Richard W. Childs, MD National Heart, Lung, and Blood Institute (NHLBI)
  More Information

Additional Information:
Publications:
Responsible Party: Richard W. Childs, National Heart, Lung, and Blood Institute
ClinicalTrials.gov Identifier: NCT00003553     History of Changes
Obsolete Identifiers: NCT00001635
Other Study ID Numbers: CDR0000066610, NHLBI-97-H-0196
Study First Received: November 1, 1999
Last Updated: June 23, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IV renal cell cancer
recurrent renal cell cancer

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Methotrexate
Cyclosporins
Cyclosporine
Fludarabine phosphate
Mycophenolate mofetil
Antilymphocyte Serum
Fludarabine
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014