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 indication is based upon response rate.
There are no trials verifying an improvement in disease-related symptoms or increased survival with Clolar.
Important Safety Information Clolar® (clofarabine injection)
Warnings and Precautions
Clolar causes myelosuppression which may be severe and prolonged.
Febrile neutropenia occurred in 55% and non-febrile neutropenia in an additional 10% of pediatric patients in clinical trials.
Myelosuppression is usually reversible with interruption of Clolar treatment and appears to be dose-dependent.
Monitor complete blood counts.
Serious and fatal hemorrhage, including cerebral, gastrointestinal and pulmonary hemorrhage, has occurred. The majority of the cases were associated with thrombocytopenia. Monitor platelets and coagulation parameters and treat accordingly.
Clolar increases the risk of infection, including severe and fatal sepsis, and opportunistic infections.
A total of 83% of patients experienced at least one infection after Clolar treatment, including fungal, viral and bacterial infections.
Monitor patients for signs and symptoms of infection, discontinue Clolar, and treat promptly.
Hyperuricemia (Tumor Lysis)
Administration of Clolar may result in tumor lysis syndrome associated with the break-down metabolic products from peripheral leukemia cell death.
Monitor patients undergoing treatment for signs and symptoms of tumor lysis syndrome and initiate preventive measures including adequate intravenous fluids and measures to control uric acid.
Systemic Inflammatory Response Syndrome (SIRS) and Capillary Leak Syndrome
- Clolar may cause a cytokine release syndrome (e.g., tachypnea, tachycardia, hypotension, pulmonary edema) that may progress to the systemic inflammatory response syndrome (SIRS) with capillary leak syndrome and organ impairment which may be fatal. Monitor patients frequently for these conditions.
In clinical trials, SIRS was reported in two patients (2%); capillary leak syndrome was reported in four patients (4%).
Symptoms included rapid onset of respiratory distress, hypotension, pleural and pericardial effusion, and multi-organ failure.
Close monitoring for this syndrome and early intervention may reduce the risk.
Immediately discontinue Clolar and provide appropriate supportive measures.
The use of prophylactic steroids may be of benefit in preventing signs or symptoms of SIRS or capillary leak.
Consider use of diuretics and/or albumin.
Venous Occlusive Disease of the Liver
Patients who have previously received a hematopoietic stem cell transplant (HSCT) are at higher risk for veno-occlusive disease (VOD) of the liver 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 a combination study of clofarabine in pediatric patients with relapsed or refractory acute leukemia.
Two cases (2%) of VOD in the mono-therapy studies were considered related to study drug.
Monitor for and discontinue Clolar if VOD is suspected.
Severe and fatal hepatotoxicity, including hepatitis and hepatic failure, has occurred with the use of Clolar.
In clinical studies, Grade 3-4 liver enzyme elevations were observed in pediatric patients during treatment with Clolar at the following rates:
elevated aspartate aminotransferase (AST) occurred in 36% of patients; elevated alanine aminotransferase (ALT) occurred in 44% of patients.
Monitor hepatic function and for signs and symptoms of hepatitis and hepatic failure.
Discontinue Clolar for Grade 3 or greater liver enzyme and/or bilirubin elevations.
In clinical studies, Grade 3 or 4 elevated creatinine occurred in 8% of patients;
acute renal failure was reported as Grade 3 in three patients (3%) and Grade 4 in two patients (2%).
Hematuria was observed in 13% of patients overall. Monitor patients for renal toxicity and interrupt or discontinue Clolar as necessary.
Fatal and serious cases of enterocolitis, including neutropenic colitis, cecitis, and C. difficile colitis, have occurred during treatment with clofarabine. This has occurred more frequently within 30 days of treatment, and in the setting of combination chemotherapy. Enterocolitis may lead to necrosis, perforation, hemorrhage or sepsis complications. Monitor patients for signs and symptoms of enterocolitis and treat promptly.
Serious and fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported. Discontinue Clofarabine for exfoliative or bullous rash, or if SJS or TEN is suspected.
Clolar can cause fetal harm when administered to a pregnant woman.
Women of childbearing potential should be advised to avoid becoming pregnant while receiving Clolar.
- Female patients should be advised to avoid breast-feeding during treatment with Clolar.
Incidence of Treatment Emergent Laboratory Abnormalities (All Grades)
||Grade 3 or higher
|Elevated total bilirubin
- Most common adverse reactions (≥10%) 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%).
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