Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

Basic Trial Information

Special Category: NIH Clinical Center trial

Objectives

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

Entry 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

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

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

Expected Enrollment

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

Outcomes

Graft vs tumor effect as measured by CT scan at days 30, 60, and 100 following transplant

Disease-free survival as measured by CT scan at 6 months and 1 year

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.

Childs R, Chernoff A, Contentin N, et al.: Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 343 (11): 750-8, 2000.[PUBMED Abstract]

Carvallo C, Geller N, Kurlander R, et al.: Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood 103 (4): 1560-3, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Heart, Lung, and Blood Institute

Richard Childs, MD, Protocol chair		Ph: 301-594-8008 Email: childsr@nih.gov

U.S.A.
Maryland
	Bethesda
	NIH - Warren Grant Magnuson Clinical Center
		Patient Recruitment	Ph:  800-411-1222

Registry Information
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
Trial Start Date		1999-01-05
Trial Completion Date		2009-12-30 (estimated)
Registered in ClinicalTrials.gov		NCT00003553
Date Submitted to PDQ		1998-08-12
Information Last Verified		2009-06-21

Back to Top