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

November 1, 1999
June 23, 2009
January 1999
December 2009   (final data collection date for primary outcome measure)
Graft vs tumor effect as measured by CT scan at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00003553 on ClinicalTrials.gov Archive Site
Disease-free survival as measured by CT scan at 6 months and 1 year [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer
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

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.

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.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
Kidney Cancer
  • Biological: anti-thymocyte globulin
    Given IV
  • Drug: cyclophosphamide
    Given IV
  • Drug: cyclosporine
    Given IV
  • Drug: fludarabine phosphate
    Given IV
  • Drug: methotrexate
    Given as GVHD prophylaxis
  • Drug: mycophenolate mofetil
    Given as GVHD prophylaxis
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
  • 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.

    Interventions:
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
  • 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.
    Interventions:
    • Biological: anti-thymocyte globulin
    • Drug: cyclophosphamide
    • Drug: fludarabine phosphate
  • 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.
    Intervention: Drug: cyclosporine
  • 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.
    Interventions:
    • Drug: cyclosporine
    • Drug: mycophenolate mofetil
  • Experimental: GVHD regimen 3 (open to accrual as of 2/11/02)
    Patients receive cyclosporine as in regimen 1. Patients also receive methotrexate.
    Interventions:
    • Drug: cyclosporine
    • Drug: methotrexate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
80
Not Provided
December 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 80 Years
No
Not Provided
United States
 
NCT00003553
CDR0000066610, NHLBI-97-H-0196
Not Provided
Richard W. Childs, National Heart, Lung, and Blood Institute
National Heart, Lung, and Blood Institute (NHLBI)
Not Provided
Study Chair: Richard W. Childs, MD National Heart, Lung, and Blood Institute (NHLBI)
National Cancer Institute (NCI)
June 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP