Sunitinib and Irradiated Donor Lymphocytes in Treating Patients With Metastatic Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Infusing irradiated donor lymphocytes into the patient may help the patient's immune system kill tumor cells. Giving sunitinib together with irradiated donor lymphocytes may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving sunitinib together with irradiated donor lymphocytes works in treating patients with metastatic kidney cancer.

Detailed Description
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OBJECTIVES: Primary Determine progression-free survival of patients with metastatic clear cell renal cell carcinoma treated with sunitinib and irradiated allogeneic lymphocytes. Secondary Determine rates and kinetics of clinical/radiographic response in these patients. Determine toxicities associated with treatment in these patients. Assess stable disease at 6 months in these patients. Assess overall survival of these patients. OUTLINE: Patients receive oral sunitinib malate once daily for 4 weeks. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity. Beginning with course 2 of sunitinib malate, patients also receive irradiated allogeneic lymphocytes IV over 1 hour every 8-16 weeks for up to 6 infusions in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 60 days.

Official Title
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Phase II Study of Sunitinib Plus Extended Courses of Irradiated Allogeneic Lymphocytes for Patients With Renal Cell Carcinoma (SPECIAL Trial)

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: therapeutic allogeneic lymphocytes
* Drug: sunitinib malate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma Primary lesion or metastatic site demonstrating clear cell variant with < 25% of any other histology Radiographically measurable disease by RECIST criteria Initiated treatment with sunitinib malate ≤ 6 weeks ago No radiographically detectable brain metastases by MRI or CT scan HLA-partially matched related donor available, as determined by serologic and/or DNA typing Appropriate HLA match (≥ 2/6 HLA A, B, DR match) PATIENT CHARACTERISTICS: ECOG performance status 0-1 Absolute neutrophil count > 1,500/mm³ Platelet count > 100,000/mm³ Total bilirubin ≤ 2.0 times upper limit of normal (ULN) AST ≤ 3.0 times ULN Calculated creatinine clearance ≥ 40 mL/min Cardiac ejection fraction ≥ 50% QTc interval < 500 msec by EKG Not pregnant Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity None of the following within the past 6 months: Myocardial infarction Severe/unstable angina Coronary/peripheral artery bypass graft Symptomatic congestive heart failure Cerebrovascular accident or transient ischemic attack Pulmonary embolism No ongoing ventricular cardiac dysrhythmias ≥ grade 2, according to NCI CTCAE v3.0 No history of serious ventricular arrhythmia (e.g., ventricular tachycardia > 3 beats in a row) No ongoing atrial fibrillation No other malignancies within the past 3 years, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, or ductal or lobular carcinoma in situ of the breast No other concurrent serious illness PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior systemic therapy for metastatic renal cell carcinoma No prior immunotherapy No prior VEGF-targeted or mTOR-targeted therapies No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), St. John's wort, ketoconazole, dexamethasone, dysrhythmic drugs (e.g., terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice No other concurrent investigational anticancer agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib plus Irradiated Allogeneic Lymphocytes<br> | Biological: therapeutic allogeneic lymphocytes<br>* Patients with a partially HLA-matched family member who can serve as a hematopoietic stem cell transplant donor will receive partially HLA-matched irradiated donor lymphocytes approximately every 8 weeks depending upon response<br>Drug: sunitinib malate<br>* Sunitinib will be administered orally at a dose of 50 mg qd for 4 consecutive weeks followed by 2 weeks off for every cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Determined as the time from treatment with combination sunitinib with irradiated allogeneic lymphocytes to progressive disease or death whichever occurred first. Progression is determined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) as 20% increase in the sum of the of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, on average up to 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per response evaluation criteria in solid tumors criteria (RECIST v 1.0) for target lesions and assessed by MRI; Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Stable disease - not meeting criteria for response or progression. | Best responseFrom date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clear cell renal cell carcinoma, stage IV renal cell cancer