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Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment

NCT01698879 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 46

Last updated 2021-01-27

Study results available
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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.

Conditions

  • Novo Acute Myeloid Leukemia

Interventions

DRUG

Mylotarg

Cohort 1 version 1.0. GO: 6mg/m\^2 (maximum 10 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m\^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m\^2 IV days 1 to 7, to begin 4 hours after the administration of GO. Cohort 1.0 version 2.0: GO: 3 mg/m\^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m\^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m\^2 IV days 1 to 7, to begin 4 hours after the administration of GO. Cohort 2: G-CSF: 150 mcg/m\^2, SC, days 0 to 7. GO: 3 mg/m\^2 (maximum 5 mg), IV infusion, 2 hours, day 1. Idarubicin: 12 mg/m\^2, IV, 30 minutes, on days 2, 3, 4. Cytarabine: 100 mg/m\^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.

Sponsors & Collaborators

  • Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

    lead OTHER

Principal Investigators

  • Jordi Sierra, MD · Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2009-10-31
Primary Completion
2016-09-14
Completion
2016-09-26

Countries

  • Spain

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01698879 on ClinicalTrials.gov