Hydroxychloroquine and Aldesleukin in Treating Patients With Metastatic Kidney Cancer

Inclusion Criteria

• Histologically confirmed metastatic renal cell carcinoma with predominantly clear cell histology
• Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria; for example, this would include tumor in the lung, liver, and retroperitoneum; bone disease is difficult to follow and quantify and as a sole site would not be acceptable
• Patients must be at least 4 weeks from radiation or surgery and recovered from all ill effects
• Age ≥ 18 years
• Karnofsky performance status >= 80%
• Absolute neutrophil count (ANC) >= 1000 cells/uL
• Platelets >= 100,000/uL
• Hemoglobin >= 9 g/dl (pre transfusion values used for prognostic factor, can be transfused or use recombinant erythropoietin growth factors but must not have active bleeding)
• Aspartate aminotransferase (AST) =< 2 x ULN (upper limit of normal)
• Serum total bilirubin =< 2 x ULN (except for patients with Gilbert’s Syndrome)
• Serum creatinine =< 1.5 mg/dL or estimated creatinine clearance >= 60 ml/min using Crockcroft-Gault estimation
• Forced expiratory volume in 1 second (FEV1) >= 2.0 liters or >= 75% of predicted for height and age; (pulmonary function tests (PFTs) are required for patients over 50 or with significant pulmonary or smoking history defined as > 20 pack years or history of chronic obstructive pulmonary disease [COPD]/emphysema)
• No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than one year prior to entry, serious cardiac arrhythmias, or unstable angina; patients who are over 40 or have had previous cardiac disease will be required to have a negative or low probability cardiac stress test for cardiac ischemia
• Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study
• Appropriate contraception in both genders (i.e., use of contraceptive strategies that prevent pregnancy; this most effectively would involve abstinence during the period of treatment but could include contraceptives, contragestives, and barrier methods.)
• The patient must be competent and have signed informed consent
• No history of cerebrovascular accident, transient ischemic attacks, central nervous system or brain metastases

Exclusion Criteria

• Patients who have previously received IL-2 are not eligible. Patients on hydroxychloroquine (HCQ) in neoadjuvant protocols or in the past for clinical indications ARE eligible, as are patients who have previously received CTLA-4 and/or PD-1/PD-L1 antibodies
• Concomitant second malignancy except for non-melanoma skin cancer, and non-invasive cancer such as cervical carcinoma in situ (CIS), superficial bladder cancer without local recurrence or breast CIS
• In patients with a prior history of invasive malignancy, less than five years in complete remission
• Positive serology for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
• Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen
• Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 2 weeks must have passed since the last dose)
• History of inflammatory bowel disease or other serious autoimmune disease; (not including thyroiditis and rheumatoid arthritis); patients already on hydroxychloroquine for such disorders are not eligible
• Patients with organ allografts
• Uncontrolled hypertension (blood pressure [BP] > 150/100 mmHg)
• Proteinuria dipstick > 3+ or >= 2 gm/24 hours
• Urine protein:creatinine ratio >= 1.0 at screening
• Major surgery, open biopsy, significant traumatic injury within 28 days of starting treatment or anticipation of need for major surgical procedure during the course of the study
• Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to starting treatment; central venous catheter placements are permitted
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to starting treatment
• Serious, non-healing wound, ulcer, or bone fracture
• History of tumor-related or other serious hemorrhage, bleeding diathesis, or underlying coagulopathy
• History of deep venous thrombosis, clinically significant peripheral vascular disease, or other thrombotic event
• Inability to comply with study and/or follow-up procedures
• Individuals with known history of glucose 6 phosphate deficiency are excluded from the trial (possible issue with HCQ tolerance). No literature can be found to support hemolytic anemia having ever occurred in these patients and rheumatologists who frequently utilize this drug have not seen this as a side effect. Given that this has been a concern that has been raised, we believe it is prudent to exclude these patients with known glucose 6 phosphate dehydrogenase (G6PD) deficiency from participation. These patients can receive IL-2 alone off trial
• Patients with previously documented macular degeneration or diabetic retinopathy are excluded from the trial
• Baseline electrocardiogram (EKG) with corrected QT interval (QTc) > 470 msec (including subjects on medication); subjects with ventricular pacemaker for whom QT interval is not measurable will be eligible on a case-by-case basis