Phase I-II study of bendamustine in patients with acute leukemia and high risk myelodysplastic syndrome.

Abstract

UNLABELLED:

A phase I-II study of bendamustine fractionated twice daily schedule for 4 days identified 75 mg/m(2) intravenously(IV) twice daily for 4 days as a phase II study schedule.

BACKGROUND:

Alkylating agents have shown activity in leukemia. Bendamustine, an active alkylating agent in lymphoma and chronic lymphocytic leukemia, was given in a fractionated twice daily schedule for 4 days to patients with acute leukemia and myelodysplastic syndrome (MDS) to define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD).

PATIENTS AND METHODS:

Adults with refractory acute leukemia or high-risk MDS were treated with bendamustine at a starting dose of 50 mg/m(2) IV over 1-2 hours twice daily for 4 days. Dose escalations were by 25 mg/m(2) in the 1st 3 levels. The study used the 3 + 3 design.

RESULTS:

A total of 25 patients were treated. Their median age was 57 years; the median salvage number was 3. Grade 2 creatinine elevations were observed in 1 of 6 patients at the 50 mg/m(2) dose, in 2 of 13 patients at the 75 mg/m(2) dose, and in 3 of 6 patients at the 100 mg/m(2) dose. This was considered significant, even though DLT was not reached. One patient achieved marrow complete remission. Significant reductions of marrow blasts (50% or more) were observed in 6 of 25 patients (24%).

CONCLUSION:

Bendamustine fractionated dose level of 100 mg/m(2) IV twice daily for 4 days (800 mg/m(2) per course) was associated with Grade 2 renal toxicity. The proposed phase II schedule is 75 mg/m(2) IV twice daily for 4 days. Future studies should evaluate this schedule in less heavily treated patients.

• Authors: Christelle Chacar, Elias Jabbour, Farhad Ravandi, Gautam Borthakur, Tapan Kadia, Zeev Estrov, Mary Beth Rios, Jorge Cortes, Hagop Kantarjian
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 12 Issue 3 Pg. 197-200 (Jun 2012) ISSN: 2152-2669 [Electronic] United States
• PMID: 22578814 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• Nitrogen Mustard Compounds
• Bendamustine Hydrochloride

Topics

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents, Alkylating (administration & dosage, adverse effects, therapeutic use)
• Bendamustine Hydrochloride
• Female
• Humans
• Leukemia (drug therapy)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy)
• Nitrogen Mustard Compounds (administration & dosage, adverse effects, therapeutic use)
• Treatment Outcome
• Young Adult