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Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer

This study is currently recruiting participants.
Information provided by National Cancer Institute (NCI)

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Descriptive Information Fields
Brief Title  Peripheral Stem Cell Transplant in Treating Patients With Metastatic Kidney Cancer
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
Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, 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.

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

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: This is a dose-escalation study of a conditioning regimen. (Dose escalation completed as of 10/1/03.)

Patients receive 1 of 3 dose levels of conditioning chemotherapy prior to peripheral blood progenitor cell (PBPC) transplantation. (Dose levels 2 and 3 are closed to accrual as of 10/1/03.)

  • Dose level 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes daily on days -5 to -1.
  • Dose level 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 daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2.
  • Dose level 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour daily on days -8 to -6, fludarabine IV over 30 minutes daily on days -5 to -1, and antithymocyte globulin daily on days -5 to -2.

Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may be repeated on days 1 and 2 if deemed necessary.

Patients with progressive disease on days 15-30, day 60, or day 100, without graft-versus-host disease, 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 2.5 years.

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

Study Phase Phase II
Study Type  Interventional
Study Design  Treatment, Open Label
Primary Outcome Measure  Graft vs tumor effect by CAT scan at days 30, 60, and 100 following transplant [ Designated as safety issue: No ]
Secondary Outcome Measure  Disease-free survival by CAT scan at 6 months and 1 year [ Designated as safety issue: No ]
Condition  Kidney Cancer
Intervention  Drug: anti-thymocyte globulin
Drug: cyclophosphamide
Drug: fludarabine phosphate
MEDLINE PMIDs 10984562,   14551148
Links Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site
Recruitment Information Fields
Recruitment Status  Recruiting
Enrollment  80
Start Date  January 1999
Completion Date
Eligibility 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
Gender Both
Ages 18 Years to 80 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries  United States
Administrative Information Fields
NCT ID  NCT00003553
Organization ID CDR0000066610
Secondary IDs †† NHLBI-97-H-0196
Study Sponsor  National Heart, Lung, and Blood Institute (NHLBI)
Collaborators ††
Investigators 
Study Chair:     Richard W. Childs, MD     National Heart, Lung, and Blood Institute (NHLBI)    
Information Provided By National Cancer Institute (NCI)
Verification Date March 2008
First Received Date  November 1, 1999
Last Updated Date June 11, 2008

 †    Required WHO trial registration data element.
††   WHO trial registration data element that is required only if it exists.




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