Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Peripheral Stem Cell Transplantation in Treating Patients With Metastatic or Recurrent Kidney Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 to 65	NCI	FCCC-01006 TUHSC-3721, NCI-G01-2021, NCT00025519

Objectives

1. Determine the feasibility of submyeloablative HLA-identical allogeneic peripheral blood stem cell transplantation in patients with metastatic or recurrent renal cell carcinoma.
2. Determine the toxicity of this regimen, in terms of incidence and severity of graft rejection, acute graft-vs-host disease (GVHD), chronic GVHD, adverse effects from the preparative regimen and thalidomide, and infection and bleeding, in these patients.
3. Determine the efficacy of this regimen, in terms of objective partial and complete response rates, in these patients.
4. Determine the engraftment rates and extent of chimerism in patients treated with this regimen.
5. Determine the overall survival and time to treatment failure rate in patients treated with this regimen.
6. Determine the impact of thalidomide on the treatment of chronic GVHD in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed renal cell carcinoma (RCC)
  • Histology demonstrates major clear cell component
  • Metastatic (stage IV) or recurrent disease
• Prior debulking nephrectomy required
  • Disease not amenable to complete surgical resection
• Must have HLA-identical donor
  • Matched related sibling donors must have 6/6 serologic HLA A, B, and DR match with molecular confirmation at DRB1
    • A 5/6 serologic mismatch with one antigen mismatch at locus A or B (not DR) with molecular confirmation at locus A, B, and DRB1 allowed
  • Matched unrelated donors must have a minimum of 8 out of 10 molecular matches at loci A, B, C, DRB1, and DQB1
• No brain metastases
  • Negative MRI required

Prior/Concurrent Therapy:

Biologic therapy:

• Prior interleukin-2 allowed
• Prior interferon alfa allowed

Chemotherapy:

• Prior chemotherapy allowed
• No other concurrent chemotherapy for RCC

Endocrine therapy:

• No concurrent corticosteroids for other comorbid disease

Radiotherapy:

• No prior extensive radiotherapy to marrow microenvironment greater than 20% of total marrow mass
• No prior radiotherapy that has reached tissue tolerance for heart, lung, liver, kidney, or spinal cord

Surgery:

• See Disease Characteristics

Other:

• No other concurrent therapy for RCC
• No concurrent enrollment on another investigational protocol for treatment of RCC
• No other concurrent immunosuppressive medications
• No other concurrent investigational drugs

Patient Characteristics:

Age:

• 18 to 65

Performance status:

• Karnofsky 80-100%

  OR

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• ALT/AST less than 2 times ULN
• Alkaline phosphatase less than 2 times ULN
• Hepatitis A, B, and C negative

Renal:

• Creatinine clearance greater than 50 mL/min
• Calcium less than 10.5 mg/dL (bisphosphonates allowed)

Cardiovascular:

• LVEF no less than 10% below lower limit of normal

Pulmonary:

• FEV₁ and DLCO greater than 50%

Other:

• HIV negative
• No active bacterial, fungal, or viral (including cytomegalovirus) infections
• No intolerance or allergy to tacrolimus, mycophenolate mofetil, or fludarabine
• No intolerance to 200 cGy of total body irradiation
• No other serious comorbid disease, neurologic condition, or psychosocial condition that would preclude study follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for at least 1 month before, during, and for at least 3 months after study participation

Expected Enrollment

A maximum of 20-40 patients (10-20 per stratum) will be accrued for this study.

Outline

Patients are stratified according to risk (low vs high).

Patients receive fludarabine IV over 30 minutes once daily on days -4 to -2 followed by total body irradiation on day -1. Patients receive tacrolimus IV over 24 hours or orally daily on days -3 to 35 and oral mycophenolate mofetil twice daily on days -3 to 28 as graft-vs-host disease (GVHD) prophylaxis. Patients undergo allogeneic peripheral blood stem cell transplantation over 1-2 hours on day 0.

Patients maintaining a mixed chimerism with no evidence of grade III or IV GVHD receive donor lymphocyte infusions (DLI) on days 60, 90, and 120. Patients may receive additional DLI as needed. Patients with limited chronic GVHD receive oral thalidomide daily beginning after day 80 and continuing for 1 year or until disease progression or resolution of chronic GVHD.

Patients are followed at 1, 3, 6, and 12 months and then every 6 months thereafter.

Trial Contact Information

Trial Lead Organizations

Fox Chase Cancer Center - Philadelphia

Gary Hudes, MD, Protocol chair		Ph: 215-728-2984; 888-369-2427

Registry Information
Official Title		Submyeloablative Allogeneic Blood Stem Cell Transplantation with HLA Identical Donor Lymphocyte Infusions from Matched Related and Matched Unrelated Donors for Treatment of Metastatic Renal Cell Carcinoma
Trial Start Date		2001-06-01
Trial Completion Date		2006-10-10
Registered in ClinicalTrials.gov		NCT00025519
Date Submitted to PDQ		2001-08-17
Information Last Verified		2005-08-20
NCI Grant/Contract Number		CA06927

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