Phase II study of methotrexate, vincristine, pegylated-asparaginase, and dexamethasone (MOpAD) in patients with relapsed/refractory acute lymphoblastic leukemia

Am J Hematol. 2015 Feb;90(2):120-4. doi: 10.1002/ajh.23886. Epub 2014 Nov 19.

Abstract

Newer approaches are needed for the treatment of relapsed and refractory acute lymphoblastic leukemia (ALL). Asparaginase-based regimens are active in the treatment of pediatric ALL and may be important in salvage therapy for adult patients. We conducted a pilot trial combining methotrexate, vincristine, PEGylated-asparaginase, and dexamethasone (MOpAD) in adults with relapsed or refractory ALL. We added tyrosine kinase inhibitors in patients with Philadelphia chromosome positive (Ph+) ALL and rituximab in patients with CD20 positive B-cell ALL. Among 37 patients treated (median age 42 years; median 2 prior therapies), the complete remission (CR) rate was 28% and an overall response rate (ORR) was 39%. The median CR duration was 4.3 months. Patients with Ph+ ALL had CR and ORR of 50% and 67%, respectively and the CR and ORR in patients with T-cell leukemia were 45% and 56%, respectively. The median survival in patients with CR/CRp was 10.4 versus 3.4 months in nonresponders (P = 0.02). The most common grade 3 or 4 nonhematologic toxicities were elevations in bilirubin and transaminases, nausea, peripheral neuropathy, and hyperglycemia, which were managed with supportive care, dose adjustments, and interruptions.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols*
  • Asparaginase / administration & dosage
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / pathology
  • Bilirubin / blood
  • Dexamethasone / administration & dosage
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Pilot Projects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Protein Kinase Inhibitors / administration & dosage
  • Recurrence
  • Rituximab
  • Survival Analysis
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / pathology
  • Transaminases / blood
  • Treatment Outcome
  • Vincristine / administration & dosage

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Protein Kinase Inhibitors
  • Rituximab
  • Vincristine
  • Dexamethasone
  • Transaminases
  • Asparaginase
  • Bilirubin
  • Methotrexate