Clofarabine with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming for relapsed and refractory acute myeloid leukaemia

• Published in: British journal of haematology Vol. 155; no. 2; pp. 182 - 189
• Main Authors: Becker, Pamela S., Kantarjian, Hagop M., Appelbaum, Frederick R., Petersdorf, Stephen H., Storer, Barry, Pierce, Sherry, Shan, Jianqin, Hendrie, Paul C., Pagel, John M., Shustov, Andrei R., Stirewalt, Derek L., Faderl, Stephan, Harrington, Elizabeth, Estey, Elihu H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2011; Blackwell
• Subjects: Adult; Age; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemical and Drug Induced Liver Injury - etiology; Chemotherapy; clinical trial phase 1; clinical trial phase 2; cytarabine; Cytarabine - administration & dosage; Cytarabine - adverse effects; Female; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - adverse effects; Hematologic and hematopoietic diseases; Humans; Infections - etiology; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes (neutrophilic); Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Multivariate analysis; Platelets; Proportional Hazards Models; Recurrence; Remission; Remission Induction; Risk; Salvage Therapy; Toxicity; Young Adult; Antineoplastic agent; Acute myelogenous leukemia; Relapse; remission induction; Multivariate analysis; Granulocyte colony stimulating factor; Cytarabine; Phase II trial; Nucleoside analog; Clinical trial; Remission; salvage therapy; Pyrimidine nucleoside; High dose; Treatment resistance; Hematology; Priming; Malignant hemopathy; Clofarabine; Antimetabolic; Phase I trial; Salvage treatment; clinical trial phase 2; Cancer; clinical trial phase 1
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2011.08831.x

Summary
This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose‐limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2 per day with cytarabine 2 g/m2 per day, each for 5 d, and G‐CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31–61%) and the CR + CR but with a platelet count <100 × 109/l rate was 61% (95% CI 45–75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.