Phase I study of Irofulven (MGI 114), an acylfulvene illudin analog, in patients with acute leukemia

Francis Giles, Jorge Cortes, Guillermo Garcia-Manero, Stephen Kornblau, Elihu Estey, Monica Kwari, Anthony Murgo, Hagop Kantarjian

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Irofulven (MGI 114, 6-hydroxymethylacylfulvene, HMAF) is a semisynthetic illudin analog with broad in vitro anti-neoplastic activity. In this leukemia phase I study, we investigated the toxicity profile and activity of Irofulven in patients with primary refractory or relapsed acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndromes (MDS). Irofulven was given as an intravenous infusion over five minutes daily for five days. The starting dose was 10 mg/m2/day (50 mg/m2/course). Courses were scheduled to be given every 3-4 weeks according to toxicity and antileukemic efficacy. Twenty patients {AML: 17 patients; MDS: one patient; ALL: one patient; mixed lineage acute leukemia: one patient} were treated. Nausea, vomiting, hepatic dysfunction, weakness, renal dysfunction, and pulmonary edema were dose limiting toxicities, occurring in two of five patients treated at 20 mg/m2/day and two of three patients treated at 12.5 mg/m2/day. The MTD was defined as 10mg/m2/day for five days. One patient with primary resistant AML achieved complete remission. Proposed phase II studies will further define the activity of Irofulven in patients with better prognosis AML and in other hematological malignancies, both as a single agent and in combination regimens, particularly with topoisomerase 1 inhibitors.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalInvestigational New Drugs
Issue number1
StatePublished - 2001
Externally publishedYes


  • Acute leukemia
  • Acylfulvene
  • Illudins
  • Irofulven
  • MGI 114
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)


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