clofarabine + etoposide + cyclophosphamide

The combination of clofarabine, etoposide, and cyclophosphamide (sometimes referred to as CLOVE or CEC) is a chemotherapy regimen used primarily for treating relapsed or refractory acute leukemia in pediatric patients. This combination has shown promising results in clinical trials for children with difficult-to-treat leukemias. ## Composition and Mechanism This combination therapy works through multiple mechanisms. Clofarabine inhibits DNA polymerase α and ribonucleotide reductase while also disrupting mitochondrial membrane integrity, leading to the release of proapoptotic factors that cause cell death in both dividing and non-dividing lymphocytes[3]. The synergistic antileukemic effect of this combination is based on clofarabine-mediated inhibition of the repair of DNA damage induced by cyclophosphamide and etoposide[3]. In typical dosing regimens, patients receive: - Clofarabine: 40 mg/m²/day - Etoposide: 100 mg/m²/day - Cyclophosphamide: 440 mg/m²/day These are usually administered for 5 consecutive days during induction cycles, followed by 4-day consolidation cycles[1][2]. ## Clinical Evidence Multiple studies have demonstrated the efficacy of this combination: - A study of 40 children (16 with AML, 24 with ALL) showed response rates of 44% in AML patients and 42% in ALL patients[1]. - Another study reported an overall response rate of 64% across both ALL and AML patients, with a 55% response rate specifically in ALL patients[5]. - An Italian study using a slightly modified dosing regimen (clofarabine 40 mg/m²/day, cyclophosphamide 400 mg/m²/day, and etoposide 150 mg/m²/day) reported a 56% overall response rate, with notably higher responses in B-cell ALL patients (13 out of 17 patients)[5]. ## Side Effects Common adverse events associated with this combination include: - Infections and febrile neutropenia - Gastrointestinal toxicity (diarrhea, abdominal pain) - Hepatic toxicity - Muscle pain with functional impairment (responsive to gabapentin and prednisone therapy)[2] Some protocols add prednisone (0.5 mg/kg/day) to prevent systemic inflammatory response syndrome (SIRS)[2]. ## Development Status This combination has been studied in multiple clinical trials, including phase I and II studies. It appears to be primarily used as a salvage therapy for heavily pretreated pediatric patients with relapsed or refractory acute leukemia, particularly to achieve remission before proceeding to hematopoietic stem cell transplantation[1][2]. A newer variation of this regimen replaces cyclophosphamide with bendamustine, aiming to reduce unwanted side effects while maintaining efficacy[10].

Other names

CLOVE regimenCLOVE protocolClofarabine VP 16 ciclophospahamide