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

Sponsor

Fox Chase Cancer Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00025519

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Sometimes the transplanted cells can be rejected by the body's tissues. Mycophenolate mofetil, tacrolimus, and donor white blood cells may prevent this from happening.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by peripheral stem cell transplantation in treating patients who have metastatic or recurrent kidney cancer.

Condition or Disease	Intervention/Treatment	Phase
Kidney Cancer	Biological: therapeutic allogeneic lymphocytes Drug: fludarabine phosphate Drug: mycophenolate mofetil Drug: tacrolimus Drug: thalidomide Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the feasibility of submyeloablative HLA-identical allogeneic peripheral blood stem cell transplantation in patients with metastatic or recurrent renal cell carcinoma.
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.
Determine the efficacy of this regimen, in terms of objective partial and complete response rates, in these patients.
Determine the engraftment rates and extent of chimerism in patients treated with this regimen.
Determine the overall survival and time to treatment failure rate in patients treated with this regimen.
Determine the impact of thalidomide on the treatment of chronic GVHD in patients treated with this regimen.

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.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jun 1, 2001

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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:

FEV_1 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

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