Phase II Study of Clofarabine Monotherapy in Previously Untreated Older Adults With Acute Myeloid Leukemia and Unfavorable Prognostic Factors

Kantarjian, Hagop M.; Erba, Harry P.; Claxton, David F.; Arellano, Martha; Lyons, Roger M.; Kovascovics, T.J.; Gabrilove, Janice; Craig, Michael; Douer, Dan; Maris, Michael B.; Petersdorf, Stephen H.; Shami, Paul J.; Yeager, Andrew M.; Eckert, Stephen; Abichandani, Rekha

doi:10.1200/jco.2009.23.3130

Cited by 187 publications

(152 citation statements)

References 37 publications

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“…6 The safety and efficacy of modified induction chemotherapy or preparative regimen for elderly patients need to be validated. [18][19][20][21][22][23][24][25] We found that decreases in GVHD-related and infection-related mortality contributed to the reduced risk of NRM. These findings are consistent with prior reports.…”

Section: Discussionmentioning

confidence: 74%

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

Kurosawa¹,

Yakushijin

Yamaguchi

et al. 2013

Bone Marrow Transplant

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Although recent improvements have been indicated in the outcome after allogeneic hematopoietic cell transplantation (allo-HCT), little information is available on how changes in transplant modalities have affected the outcomes after allo-HCT in non-remission, based on patient age, donor source and disease type. We compared the incidence and causes of non-relapse mortality (NRM) after allo-HCT in non-remission among three consecutive four-year periods using a nationwide transplant outcome registry database. A total of 3308 patients with acute leukemia in non-remission were analyzed. The risk of NRM decreased over the three periods, and the hazard ratios We found that a decrease in the incidences of death due to GVHD and infection contributed to the reduction in NRM, to which high-resolution donor-recipient HLA matching and other improvements may have contributed. As none of the subgroups showed improved survival without a reduction in NRM, the effective prevention of transplant-related complications appears to be necessary for improving outcomes after allo-HCT in non-remission.

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Section: Discussionmentioning

confidence: 74%

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

Kurosawa¹,

Yakushijin

Yamaguchi

et al. 2013

Bone Marrow Transplant

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“…In a large phase II study from the MD Anderson Cancer Center, older patients (n=112; age >60 years; median age 71 years), most of whom had additional risk factors, received clofarabine, 30 mg/m 2 intravenously for 5 days. 153 CR/CRp was achieved in 46% of patients, with a 30-day mortality rate of 10%. Patients who experienced a remission continued to receive therapy every 4 to 6 weeks to maintain remission for up to 6 additional treatment cycles.…”

Section: Induction Therapymentioning

confidence: 99%

“…For the entire patient cohort, the median DFS and OS were 37 and 41 weeks, respectively; patients experiencing a CR had a median OS of 72 weeks. 153 In a pooled analysis of data from two European phase II studies that also evaluated first-line clofarabine (30 mg/m 2 intravenously for 5 days, up to 4-6 courses) in older patients considered unsuitable for intensive chemotherapy (age ≥60 years; median age 71 years), monotherapy with clofarabine resulted in a CR in 32% of patients. 154 An additional 16% achieved CR with incomplete recovery of peripheral blood counts.…”

Section: Induction Therapymentioning

confidence: 99%

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Mizutani

Hara

Fujita

et al. 2016

Bone Marrow Transplant

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“…Demethylating agents, such as 5-azacitidine and decitabine, have consistently demonstrated CR rates of 15%-25% [30][31][32]. Single agent clofarabine in elderly patients with AML show CR rates of approximately 45% and acceptable treatment related mortality, although the median OS of the non-responders for these trials (15 weeks) was longer than reported in population studies of elderly AML [33,34]. Tipifarnib, the only other oral agent recently explored for AML patients unfit for induction, produced CR rates of less than 15% and median survival of 3 months [35,36].…”

Section: Discussiosnmentioning

confidence: 99%

Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia

et al. 2011

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Temozolomide sensitivity is determined by methylation of the O 6 -methylguanine-DNA methyltransferase (MGMT) promoter. This study assessed whether the temozolomide dose can be tailored by MGMT promoter status and whether protracted, low-dose temozolomide can ''prime'' blasts in patients with unmethylated MGMT (unMGMT). Elderly patients with high-risk AML were stratified by MGMT methylation. Patients with methylated MGMT (mMGMT) received temozolomide 200 mg/m 2 orally for 7 days every 4 weeks, while patients with unMGMT received temozolomide 100 mg/m 2 orally for 14 days followed by 200 mg/m 2 orally for 7 days every 6 weeks. Of 36 patients (median age, 75 years), 31 (86%) had an unMGMT promoter. Overall response rate for the entire cohort was 36%. Patients with mMGMT and unMGMT had similar response rates (40% vs. 29%). Median duration of response and overall survival (OS) among responders were 29 and 35 weeks, respectively. Induction deaths (ID) occurred in 25% of patients, mostly caused by disease progression. Hematological toxicities were the most common adverse event. Toxicities were similar between patients on conventional versus protracted schedules. High HCT-CI scores were predictive of lower CR rate, higher ID, and shorter OS, while bone marrow blast count <50% at screening predicted for improved responses. Temozolomide, dosed according to MGMT methylation status, demonstrated modest clinical activity in elderly patients with AML, especially in those presenting with fewer comorbidities and low disease burden. The trial was registered on www.ClinicalTrials.gov as #NCT00611247. Am. J. Hematol. 87:45-50, 2012. V

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Phase II Study of Clofarabine Monotherapy in Previously Untreated Older Adults With Acute Myeloid Leukemia and Unfavorable Prognostic Factors

Abstract: Clofarabine is an active agent with acceptable toxicity in patients age 60 years or older with untreated AML who have at least one unfavorable prognostic factor. ORR did not seem affected by the presence of multiple unfavorable prognostic factors.

Cited by 187 publications

References 37 publications

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR

Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia

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