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Clinical Trials

Proleukin has demonstrated long-lasting efficacy1-3

In clinical trials, Proleukin has demonstrated over 10 years of durable complete responses in some mRCC and mM patients. Complete response rates achieved were 7% in mRCC patients and 6% in mM patients.1-3

Pivotal mRCC clinical data
Methodology1,2:
  • 225 mRCC patients were enrolled in 7 clinical trials across 21 institutions
  • Proleukin (600,000 or 720,000 IU/kg) was administered in 15-minute infusions every 8 hours for up to 14 consecutive doses over 5 days
  • A second, identical cycle was administered, following up to 9 days of rest

Objective response rate (CRa + PRb) 15% (37/255)

Complete responses 7% (17/255)

Partial responses 8% (20/255)

Proleukin demonstrated:
  • Both durable complete responses (CRs) and partial responses (PRs)1,2
  • > 90% regression or complete disappearance of tumors in over 70% of responders with a baseline tumor of ≥ 50 cm2 4,*
  • Responses were evident in metastatic sites (including the lung, liver, lymph node, renal bed, spleen, soft tissue, and bone) regardless of visceral involvement and tumor burden1,4
remission chart

*Fourteen of 36 responders had baseline tumor burden ≥ 50 cm2; of these, 8 of 14 had > 90% tumor regression, and 2 of 14 had complete disappearance of tumors after Proleukin® treatment.4
aCR is defined as complete disappearance of tumors. One of the 17 patients with a CR relapsed at 86 months.2,4
bPR is defined as ≥ 50% reduction in measurable tumor area with no increase in the size of lesions. Two of the 20 patients with a PR remain in continuing remission > 83 and > 126 months.2,4
cThe median CR duration was still not reached at 80+ months (range: 7 to 131+ months).2

A first- or second-line treatment option for mRCC patients.5,6

References: 1. Proleukin [package insert]. Yardley, PA: Clinigen, Inc; 2019. 2. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6(suppl 1):S55-S57. 3. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6(suppl 1):S11-S14. 4. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688-696. 5. NCCN® Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Kidney cancer. Version 4.2019. April 25, 2019. www.nccn.org. Accessed November 4, 2019. 6. Rini BI, McDermott DF, Hammers H, et al. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma. J Immunother Cancer. 2016;4:81. 7. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2116.

Pivotal mM clinical data
Methodology1,3:
  • 270 mM patients were enrolled in 8 clinical trials across 22 institutions
  • Proleukin (600,000 or 720,000 IU/kg) was administered in 15-minute infusions every 8 hours for up to 14 consecutive doses over 5 days
  • A second, identical cycle was administered, following up to 9 days of rest

Objective response rate (CRa + PRb) 16% (43/270)

Complete responses 6% (17/270)

Partial responses 10% (26/270)

Proleukin demonstrated:
  • Both durable complete responses (CRs) and partial responses (PRs)1,3
  • Patients who maintained a response (CRa or PRb) for at least 2.5 years did not relapse3
  • Nearly 60% (10/17) of CRs maintained response ranging from 3.5 to 10 years3
  • Responses were evident in metastatic sites (including the lung, liver, lymph node, spleen, adrenal glands, soft tissue, bone, and in cutaneous and subcutaneous sites) regardless of visceral involvement and tumor burden1,7,c
remission chart

aCR is defined as complete disappearance of tumors. The median CR duration was still not reached at 59+ months (range: 3 to 122+ months).3,7
bPR is defined as ≥ 50% reduction in measurable tumor area with no increase in the size of lesions.3,7
cOf 17 patients with a CR, 14 were ECOG PS 0 and 3 were PS 1; of 26 patients with PR, 22 were PS 0, 3 were PS 1, and 1 was PS 2.7

References: 1. Proleukin [package insert]. Yardley, PA: Clinigen, Inc; 2019. 2. Fisher RI, Rosenberg SA, Fyfe G. Long-term survival update for high-dose recombinant interleukin-2 in patients with renal cell carcinoma. Cancer J Sci Am. 2000;6(suppl 1):S55-S57. 3. Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000;6(suppl 1):S11-S14. 4. Fyfe G, Fisher RI, Rosenberg SA, Sznol M, Parkinson DR, Louie AC. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688-696. 5. NCCN® Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Kidney cancer. Version 4.2019. April 25, 2019. www.nccn.org. Accessed November 4, 2019. 6. Rini BI, McDermott DF, Hammers H, et al. Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of renal cell carcinoma. J Immunother Cancer. 2016;4:81. 7. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2116.

EXPAND +

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC).

Summary of Important Safety Information for Proleukin® (aldesleukin) for injection, for intravenous infusion.

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC).

Summary of Important Safety Information for Proleukin® (aldesleukin) for injection, for intravenous infusion.

WARNINGS

Therapy with Proleukin® (aldesleukin) should be restricted to patients with normal cardiac and pulmonary functions as defined by thallium stress testing and formal pulmonary function testing. Extreme caution should be used in patients with a normal thallium stress test and a normal pulmonary function test who have a history of cardiac or pulmonary disease.

Proleukin should be administered in a hospital setting under the supervision of a qualified physician experienced in the use of anticancer agents. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available.

Proleukin administration has been associated with capillary leak syndrome (CLS) which is characterized by a loss of vascular tone and extravasation of plasma proteins and fluid into the extravascular space. CLS results in hypotension and reduced organ perfusion which may be severe and can result in death. CLS may be associated with cardiac arrhythmias (supraventricular and ventricular), angina, myocardial infarction, respiratory insufficiency requiring intubation, gastrointestinal bleeding or infarction, renal insufficiency, edema, and mental status changes.

Proleukin treatment is associated with impaired neutrophil function (reduced chemotaxis) and with an increased risk of disseminated infection, including sepsis and bacterial endocarditis. Consequently, preexisting bacterial infections should be adequately treated prior to initiation of Proleukin therapy. Patients with indwelling central lines are particularly at risk for infection with gram positive microorganisms. Antibiotic prophylaxis with oxacillin, nafcillin, ciprofloxacin, or vancomycin has been associated with a reduced incidence of staphylococcal infections.

Proleukin administration should be withheld in patients developing moderate to severe lethargy or somnolence; continued administration may result in coma.

INDICATION AND USAGE

Proleukin® (aldesleukin) is indicated for the treatment of adults with metastatic renal cell carcinoma (metastatic RCC).

Proleukin is indicated for the treatment of adults with metastatic melanoma.

Careful patient selection is mandatory prior to the administration of Proleukin.

Evaluation of clinical studies to date reveals that patients with more favorable ECOG performance status (ECOG PS 0) at treatment initiation respond better to Proleukin, with a higher response rate and lower toxicity. Therefore, selection of patients for treatment should include assessment of performance status.

Experience in patients with ECOG PS > 1 is extremely limited.

CONTRAINDICATIONS

Proleukin® (aldesleukin) is contraindicated in patients with a known history of hypersensitivity to interleukin-2 or any component of the Proleukin formulation.

Proleukin is contraindicated in patients with an abnormal thallium stress test or abnormal pulmonary function tests and those with organ allografts. Retreatment with Proleukin is contraindicated in patients who have experienced the following drug-related toxicities while receiving an earlier course of therapy: sustained ventricular tachycardia (≥ 5 beats), cardiac arrhythmias not controlled or unresponsive to management, chest pain with ECG changes, consistent with angina or myocardial infarction, cardiac tamponade, intubation for > 72 hours, renal failure requiring dialysis > 72 hours, coma or toxic psychosis lasting > 48 hours, repetitive or difficult to control seizures, bowel ischemia/perforation, GI bleeding requiring surgery.

WARNINGS

Because of the severe adverse events which generally accompany Proleukin® (aldesleukin) therapy at the recommended dosages, thorough clinical evaluation should be performed to identify patients with significant cardiac, pulmonary, renal, hepatic, or CNS impairment in whom Proleukin is contraindicated. Patients with normal cardiovascular, pulmonary, hepatic, and CNS function may experience serious, life-threatening or fatal adverse events. Adverse events are frequent, often serious, and sometimes fatal.

Should adverse events, requiring dose modification occur, dosage should be withheld rather than reduced.

Proleukin has been associated with exacerbation of preexisting autoimmune disease and inflammatory disorders. In some cases, the onset of new autoimmune diseases, such as vitiligo, may occur. Symptomatic hyperglycemia and/or diabetes mellitus have been reported during Proleukin therapy.

All patients should have thorough evaluation and treatment of CNS metastases and have a negative scan prior to receiving Proleukin therapy. New neurologic signs, symptoms, and anatomic lesions following Proleukin therapy have been reported in patients without evidence of CNS metastases. Neurologic signs and symptoms associated with Proleukin therapy usually improve after discontinuation of Proleukin therapy; however, there are reports of permanent neurologic defects. In patients with known seizure disorders, extreme caution should be exercised as Proleukin may cause seizures.

PRECAUTIONS

Patients should have normal cardiac, pulmonary, hepatic, and CNS function at the start of therapy. Capillary leak syndrome (CLS) begins immediately after Proleukin® (aldesleukin) treatment starts and is marked by increased capillary permeability to protein and fluids and reduced vascular tone.

Proleukin® (aldesleukin) treatment should be withheld for failure to maintain organ perfusion as demonstrated by altered mental status, reduced urine output, a fall in the systolic blood pressure below 90 mm Hg or onset of cardiac arrhythmias.

Recovery from CLS begins soon after cessation of Proleukin therapy. Usually, within a few hours, the blood pressure rises, organ perfusion is restored and reabsorption of extravasated fluid and protein begins.

Kidney and liver function are impaired during Proleukin treatment. Use of concomitant nephrotoxic or hepatotoxic medications may further increase toxicity to the kidney or liver.

Mental status changes including irritability, confusion, or depression which occur while receiving Proleukin may be due to bacteremia or early bacterial sepsis, hypoperfusion, occult CNS malignancy, or direct Proleukin-induced CNS toxicity. Patients should be evaluated for these and other causes of mental status changes. Alterations in mental status due solely to Proleukin therapy may progress for several days before recovery begins. Rarely, patients have sustained permanent neurologic deficits.

Proleukin enhancement of cellular immune function may increase the risk of allograft rejection in transplant patients.

Serious manifestations of eosinophilia involving eosinophilic infiltration of cardiac and pulmonary tissues can occur following Proleukin.

ADVERSE REACTIONS

The rate of drug-related deaths in the 255 metastatic RCC patients who received single-agent Proleukin® (aldesleukin) was 4% (11/255); the rate of drug-related deaths in the 270 metastatic melanoma patients who received single-agent Proleukin was 2% (6/270).

In clinical trials, the following life-threatening (Grade 4) adverse events were seen in > 1% of 525 patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: oliguria (6%), anuria (5%), hypotension (3%), respiratory disorder (3%), bilirubinemia (2%), coma (2%), diarrhea (2%), acidosis (1%), acute kidney failure (1%), apnea (1%), cardiovascular disorder (1%), coagulation disorders (1%), confusion (1%), creatinine increase (1%), dyspnea (1%), fever (1%), heart arrest (1%), infection (1%), myocardial infarction (1%), psychosis (1%), sepsis (1%), SGOT increase (1%), stupor (1%), supraventricular tachycardia (1%), thrombocytopenia (1%), ventricular tachycardia (1%), and vomiting (1%). From the same trials, the following adverse events (Grades 1-4) were seen in ≥ 30% of 525 patients (255 with metastatic renal cell cancer and 270 with metastatic melanoma) treated with Proleukin: hypotension (71%), diarrhea (67%), oliguria (63%), chills (52%), vomiting (50%), dyspnea (43%), rash (42%), bilirubinemia (40%), thrombocytopenia (37%), nausea (35%), confusion (34%), and creatinine increase (33%).

Please see the full Prescribing Information, including Boxed Warning, for Proleukin® (aldesleukin) for injection, for intravenous infusion.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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