Idarubicin and Cytarabine in Combination with Gemtuzumab Ozogamicin (IAGO) for Untreated Patients with High-risk MDS or AML Evolved from MDS: a Phase II Study from the EORTC and GIMEMA Leukemia Groups (protocol 06013)

Overview

Journal Ann Hematol

Specialty Hematology

Date 2015 Sep 28

PMID 26410352

Citations 4

Authors

Theo de Witte

Stefan Suciu

Liv Meert

Constantijn Halkes

Dominik Selleslag

Dominique Bron

Sergio Amadori

Roel Willemze

Petra Muus

Frederic Baron

Affiliations

Soon will be listed here.

Abstract

The primary objective of this trial was to assess the feasibility, toxicity profile, and antitumor activity of gemtuzumab ozogamicin (GO) combined with a chemotherapy remission-induction regimen in adults with untreated high-risk myelodysplastic syndrome (HR-MDS) or secondary acute myeloid leukemia (sAML). In this phase II trial, 30 patients with median age of 58 years received 1 day of GO as a 1-h infusion at the dose level of 5 mg/m(2) on day 7 of the remission-induction course further consisting of a continuous infusion of cytarabine 100 mg/m(2)/day for 10 days and idarubicin 12 mg/m(2)/day on days 1, 3, and 5. A consolidation course, consisting of intermediate-dose cytarabine (A) and idarubicin (I) followed by hematopoietic stem cell transplantation (HSCT) was planned for patients in complete remission (CR). The primary endpoints were response rate (CR/CRi) and severe toxicity rate. The secondary endpoint(s) were survival and progression-free survival (PFS) from start of treatment. Thirteen patients (43 %) achieved CR (eight patients) or CR with incomplete hematopoietic recovery (CRi) (five patients). In patients who achieved CR or CRi, the median time to recovery of neutrophils to 0.5 × 10(9)/l and of platelets to >50 × 10(9)/l was 29 and 30 days, respectively. Grade 3 to 4 severe toxicities occurred in nine patients. The most prominent was liver toxicity, as shown by elevated bilirubin levels in 16 patients and one case of nonfatal veno-occlusive disease (VOD). All 13 patients with CR/CRi received consolidation therapy, which was followed by allogeneic HSCT in five patients and autologous HSCT in three patients. According to the statistical design of the study, the idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) regimen did not show sufficient activity to warrant further exploration of this regimen in adult patients with HR-MDS or sAML.

Citing Articles

Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin.

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Patient-tailored design for selective co-inhibition of leukemic cell subpopulations.

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Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials.

Ramadan S, Suciu S, Stevens-Kroef M, Willemze R, Amadori S, de Witte T Cancers (Basel). 2020; 12(11).

PMID: 33187229 PMC: 7697114. DOI: 10.3390/cancers12113334.

Comparison of Reduced-Intensity Idarubicin and Daunorubicin Plus Cytarabine as Induction Chemotherapy for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia.

Liu H, Fu R, Li L, Wang G, Song J, Ruan E Clin Drug Investig. 2016; 37(2):167-174.

PMID: 27722823 DOI: 10.1007/s40261-016-0469-9.

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