Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment
Status:
Completed
Trial end date:
2016-09-26
Target enrollment:
Participant gender:
Summary
Acute myeloid leukemia (AML) is a neoplasm of immature hematopoietic cells (blasts) with
altered ripening capacity. Due to excessive proliferation, the blasts displace normal
hematopoietic cells and bone marrow failure appears. Leukemic cells also infiltrate
extramedullary tissues.
Following the standard chemotherapy treatment, the CR rate achieved is around 65-75% for all
patients and 15% lower when considering only patients over 65 years. Modifications to the
standard regimen consist of replacing the DNR for a cytotoxic one, modifying the dose of
ara-C or adding a third drug.
Gemtuzumab ozogamicin (Mylotarg ®) is an immunoconjugate between anti-CD33 antibody and a
cytotoxic antitumor antibiotic, calicheamicin. Mylotarg ® antibody specifically binds to
CD33, a sialic acid-dependent adhesion protein expressed in over 90% of LMA10. Mylotarg ®
selectively transports the cytotoxic agent calicheamicin into leukemic cells and
hematopoietic progenitors differentiated from the myelomonocytic line, while respecting the
pluripotent hematopoietic stem cells. Calicheamicin is released only after the fixation of
the antibody anti-CD33 and its internalization by the cell, after which binds to and damages
the DNA.
Mylotarg ® is approved in the U.S. for the treatment of CD33 positive AML in first relapse,
for patients older than 60 years non-candidates for other intensive treatment modalities.
Since the efficacy of Mylotarg ® is equivalent and its toxicity profile less than the
conventional therapy, it is logical to conduct a phase II trial exploring the role of
Mylotarg ® in the early stages of treatment of AML.
Previous experience with gemtuzumab ozogamicin in relapsed patients led to its use combined
with induction chemotherapy. The aim was to improve the CR rate reached with the latter and
reduce relapse after achieving greater leukemic cytoreduction.
Recent data from the HOVON group support that the administration of G-CSF before and during
induction chemotherapy decreases the incidence of relapse in patients with AML, particularly
those considered to have intermediate risk.
Everything mentioned above justifies to investigate the combination of GO combined with
chemotherapy with IDR and ara-C in standard 3x7 scheme and analyze the effect of
sensitization with G-CSF in patients with AML de novo. If the treatment proposed here is
effective and presents an acceptable toxicity it should be investigated.
Phase:
Phase 2
Details
Lead Sponsor:
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias