Phase 1 dose-escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemias

Summary The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enroled [28 acute myeloid leukaemia (AML), 12 acute lymphoblastic leukaemia (ALL)] in this Phase 1 dose‐escalation trial of daily‐infused clofarabine (CLO) followed by cy...

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Published inBritish journal of haematology Vol. 158; no. 2; pp. 198 - 207
Main Authors Zeidan, Amer M., Ricklis, Rebecca M., Carraway, Hetty E., Yun, Hyun D., Greer, Jacqueline M., Smith, B. Douglas, Levis, Mark J., McDevitt, Michael A., Pratz, Keith W., Showel, Margaret M., Gladstone, Douglas E., Gore, Steven D., Karp, Judith E.
Format Journal Article
LanguageEnglish
Published Oxford Blackwell Publishing Ltd 01.07.2012
Blackwell
Subjects
Age
DNA
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Summary:Summary The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enroled [28 acute myeloid leukaemia (AML), 12 acute lymphoblastic leukaemia (ALL)] in this Phase 1 dose‐escalation trial of daily‐infused clofarabine (CLO) followed by cyclophosphamide (CY) for four consecutive days (CLO‐CYx4). The median age was 48·5 years. The median number of prior regimens was 2 (range 1–5), and 6/40 patients (15%) had prior allogeneic haematopoietic stem cell transplant. 28/40 patients (70%) had adverse genetic features. 6/40 patients (15%) died within 60 d of induction (two infections, four progressive disease). The average time to neutrophil recovery (absolute neutrophil count ≥0·5 × 109/l was 34 d, (range, 17–78). The overall response rate (ORR) was 33% (13/40), with seven complete remissions (18%), four complete remissions with incomplete recovery of blood counts (10%), and two partial remissions (5%). ORR was 25% (7/28), and 50% (6/12), for AML and ALL respectively. Notably, the clinical responses were independent of dose level. 7/17 patients (41%) exhibited CLO‐mediated enhancement of CY‐induced DNA, which was associated with, but not necessary for, improved clinical outcomes. In summary, the CLO‐CYx4 regimen was well tolerated and had activity in patients with RRAL, especially relapsed ALL. Therefore, CLO‐CYx4 can be considered a salvage therapy for adults with RRALs, and warrants further investigations.
Bibliography:ArticleID:BJH9142
NCI Cancer Center - No. 2P30 CA06973-47
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Genzyme
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ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ISSN:0007-1048
1365-2141
DOI:10.1111/j.1365-2141.2012.09142.x