Treatment Considerations

Clolar should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Clolar has not been studied in patients with hepatic or renal dysfunction; its use in these patients should be undertaken only with the greatest caution.

Tumor lysis, cytokine release, SIRS/capillary leak syndrome, hyperuricemia

Clolar results in a rapid reduction in peripheral blasts. Therefore, patients should be closely monitored for signs and symptoms of tumor lysis syndrome, signs and symptoms of cytokine release (e.g. tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS)/capillary leak syndrome, and organ dysfunction.

In the event of signs and symptoms of SIRS or capillary leak syndrome, either of which can be fatal, treatment with Clolar should be discontinued immediately, and use of steroids, diuretics, and albumin considered. Clolar can be reinstituted when the patient is stable, generally with a 25% dose reduction. Patients should receive continuous IV fluids throughout the 5 days of administration to reduce the effects of tumor lysis and other adverse events. If hyperuricemia is expected, allopurinol should be administered.

In clinical trials, capillary leak syndrome or SIRS occurred in 4 of 96 pediatric patients overall (3 ALL, 1 AML). Close monitoring for this syndrome and early intervention are recommended.

Bone marrow suppression

Bone marrow suppression (including neutropenia, anemia, and thrombocytopenia) should be anticipated. This is usually reversible and appears to be dose-dependent. Use of Clolar is likely to increase the risk of infection, including severe sepsis, as a result of bone marrow suppression. Antimicrobial prophylaxis may be considered.

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Indication

Clolar is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens. This use is based on the induction of complete responses. Randomized trials demonstrating increased survival or other clinical benefit have not been conducted.

Important Safety Considerations

Clolar should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function, which is usually reversible and dose dependent, should be anticipated and is likely to increase the risk of infection, including severe sepsis. Administration of Clolar results in a rapid reduction in peripheral leukemia cells. Patients should be evaluated and monitored for signs and symptoms of tumor lysis syndrome and cytokine release (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that could develop into systemic inflammatory response syndrome (SIRS)/capillary leak syndrome, and organ dysfunction. Clolar should be discontinued immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome, either of which can be fatal, and use of steroids, diuretics, and albumin considered.

The most common adverse effects after Clolar treatment, regardless of causality, were gastrointestinal tract symptoms, including vomiting (grade 3: 8%; grade 4: 1%), nausea (grade 3: 15%; grade 4: 1%), and diarrhea (grade 3: 10%); hematologic effects, including anemia (grade 3: 70%; grade 4: 18%), leukopenia (grade 4: 99%), thrombocytopenia (grade 3: 36%; grade 4: 64%), neutropenia (grade 3: 3%; grade 4: 7%), and febrile neutropenia (grade 3: 53%; grade 4: 3%); and infection (grade 3: 56%; grade 4: 18%).

Hepato-biliary toxicities were frequently observed in pediatric patients during treatment with Clolar. The most frequently reported cardiac disorder was tachycardia (34%), which was, however, already present in 27.4% of patients at study entry. Left ventricular systolic dysfunction was also noted. Since Clolar is excreted primarily by the kidneys, drugs with known renal toxicity should be avoided during the 5 days of Clolar administration. In addition, since the liver is a known target organ for Clolar toxicity, concomitant use of medications known to induce hepatic toxicity should also be avoided.

Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, have been observed in patients treated with Clolar. Because of the pre-existing immunocompromised condition of these patients and prolonged neutropenia that can result from treatment with Clolar, patients are at increased risk for severe opportunistic infections.

Pericardial effusion was a frequent finding in these patients on post-treatment studies. Careful hematologic monitoring during therapy is important. Hepatic and renal function should be assessed prior to and during treatment with Clolar, as the liver is a target organ for Clolar toxicity and the kidneys are the predominant mode of Clolar excretion.

Patients receiving Clolar may experience vomiting and diarrhea; they should therefore be advised regarding appropriate measures to avoid dehydration. Clolar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant and avoid breastfeeding while receiving treatment with Clolar.

For more information, please consult the Full Prescribing Information (PDF).