Jane S. Ricciuti, RPh, MS


January 20, 2005

In This Article

Antineoplastic Agents

(clofarabine) Injection

Manufacturer: Genzyme Corporation

Drug Approval Classification: Original New Drug Application (Approval Date: 12/28/04)

Indication: Clolar (clofarabine) injection is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia (ALL) after at least 2 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.

Dosing: The recommended pediatric dose and schedule is 52 mg/m2 administered by intravenous infusion (IVI) over 2 hours daily for 5 consecutive days. Treatment cycles are repeated following recovery or return to baseline organ function, approximately every 2 to 6 weeks.

Clinical Summary: Clofarabine is a second-generation purine nucleoside analogue that is an inhibitor of ribonucleotide reductase and DNA polymerase. Clofarabine produces apoptosis (programmed cell death) through a direct and indirect pathway.

Clofarabine's approval is based on a single phase 2 clinical trial conducted in relapsed/refractory pediatric patients with ALL at a single dose. All patients had disease that had relapsed after and/or was refractory to 2 or more prior therapies. Most patients, 46/49 (93.8%), had received 2 to 4 prior regimens and 15/49 (30.6%) of the patients had undergone at least 1 prior transplant. The median age of the treated patients was 12 years. All patients received a dose of 52 mg/m2 daily x 5 IVI. The planned study endpoint was the rate of complete remission (CR), defined as no evidence of circulating blasts or extramedullary disease, an M1 bone marrow (< 5% blasts), and recovery of peripheral counts (platelets > 100 × 109 L and absolute neutrophil count [ANC] > 1.0 × 109 L) and complete remission in the absence of total platelet recovery (CRp), defined as meeting all criteria for CR except for recovery of platelet counts. Partial response (PR) was also determined, defined as complete disappearance of circulating blasts, an M2 bone marrow (> 5% and < 25% blasts), and appearance of normal progenitor cells or an M1 marrow that did not qualify for CR or CRp. The table below summarizes results for the pediatric ALL study.

Responses N % 95% CI
CR 6 12.2 4.6 to 24.8
CRp 4 8.2 2.3 to 19.6
PR 5 10.2 3.4 to 22.2

Adverse Effects: The most common adverse effects were gastrointestinal tract symptoms, including vomiting, nausea, and diarrhea; hematologic effects, including anemia, leukopenia, thrombocytopenia, neutropenia, and febrile neutropenia; and infection.

Pharmacokinetics: Clofarabine pharmacokinetics were studied in 40 pediatric patients aged 2 to 19 years (21 males/19 females) with relapsed or refractory ALL or acute myelocytic leukemia. At a dose of 52 mg/m2, the following was observed with clofarabine:

  • 47% bound to plasma proteins, predominantly to albumin.

  • Systemic clearance at steady-state was estimated to be 28.8 L/h/m2.

  • Volume of distribution was 172 L/m2.

  • Terminal half-life was estimated to be 5.2 hours.

No drug-drug interaction studies have been conducted.

Clolar (clofarabine) Injection Labeling


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