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 Information
Warnings and Precautions:
- Clolar should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy.
Hematologic Toxicity
- Monitor complete blood counts and platelet counts during Clolar therapy.
- Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, has been observed in patients treated with Clolar. At initiation of treatment, most patients in the clinical studies had hematological impairment as a manifestation of leukemia.
- 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.
Infections
- The use of Clolar is likely to increase the risk of infection, including severe sepsis, as a result of bone marrow suppression. Monitor patients for signs and symptoms of infection and treat promptly.
Hyperuricemia (Tumor Lysis)
- Administration of Clolar may result in a rapid reduction in peripheral leukemia cells. Evaluate and monitor patients undergoing treatment for signs and symptoms of tumor lysis syndrome. Provide intravenous infusion fluids throughout the five days of Clolar administration to reduce the effects of tumor lysis and other adverse events. Administer allopurinol if hyperuricemia (tumor lysis) is expected.
Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome
- Evaluate and monitor patients undergoing treatment with Clolar for 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.
- Discontinue Clolar immediately in the event of clinically significant signs or symptoms of SIRS or capillary leak syndrome, either of which can be fatal, and consider use of steroids, diuretics, and albumin. Re-institute Clolar when the patient is stable, generally with a 25% dose reduction. The use of prophylactic steroids may be of benefit in preventing signs and symptoms of cytokine release.
Hepatic Enzymes
- Hepato-biliary enzyme elevations were frequently observed in pediatric patients during treatment with Clolar. Some patients discontinued treatment due to hepatic enzyme abnormalities.
- Hepatic and Renal Impairment
- Clolar has not been studied in patients with hepatic or renal dysfunction. Its use in such patients should be undertaken only with the greatest caution.
- Patients who have previously received a hematopoietic stem cell transplant (HSCT) may be at higher risk for hepatotoxicity suggestive of veno-occlusive disease (VOD) following treatment with clofarabine (40 mg/m2) when used in combination with etoposide (100 mg/m2) and cyclophosphamide (440 mg/m2). Severe hepatotoxic events have been reported in an ongoing Phase 1/2 combination study of clofarabine in pediatric patients with relapsed or refractory acute leukemia.
Use in Pregnancy
- Clolar can cause fetal harm when administered to a pregnant woman. Intravenous doses of clofarabine in rats and rabbits administered during organogenesis caused an increase in resorptions, malformations, and variations. Women of childbearing potential should be advised to avoid becoming pregnant while receiving Clolar.
Nursing Mothers
- Female patients should be advised to avoid breast-feeding during treatment with Clolar.
Incidence of Treatment Emergent Laboratory Abnormalities
| Parameter | Any grade | Grade 3 or higher |
|---|
| Anemia |
83% |
75% |
| Leukopenia |
88% |
88% |
| Lymphopenia |
82% |
82% |
| Neutropenia |
64% |
64% |
| Thrombocytopenia |
81% |
80% |
| Elevated creatinine |
50% |
8% |
| Elevated SGOT |
74% |
36% |
| Elevated SGPT |
81% |
43% |
| Elevated total bilirubin |
45% |
13% |
Adverse Reactions:
- Most common adverse reactions with Clolar® were nausea (73%), vomiting (78%), diarrhea (56%), febrile neutropenia (55%), headache (43%), rash (38%), pruritus (43%), pyrexia (39%), fatigue (34%), palmar-plantar erythrodysesthesia syndrome (16%), anxiety (21%), flushing (19%), and mucosal inflammation (16%).
For more information, please consult the full Prescribing Information(PDF).