This trial is active, not recruiting.

Condition novo acute myeloid leukemia
Treatment mylotarg
Phase phase 2
Target CD33
Sponsor Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Start date October 2009
End date December 2016
Trial size 40 participants
Trial identifier NCT01698879, 2007-006295-11, ICOG-07


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Idarubicin, cytarabine, Mylotarg, G-CSF.
Cohort 1 (20 evaluable patients): 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 (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours after the administration of GO. Cohort 2 (20 evaluable patients): G-CSF: 150 mcg/m^2, SC, days 0 to 7, to begin 12 to 18 hours before treatment with Gemtuzumab. 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 (cytosine arabinoside): 100 mg/m^2 IV continuous infusion on days 1 to 7, to begin 4 hours later after the administration of GO.

Primary Outcomes

Complete Remission of the Disease
time frame: 28 days after chemotherapy

Secondary Outcomes

Secondary Toxicity to Mylotarg(R)
time frame: Baseline, weekly during treatment and at month 3 and month 6 after first induction.
Mortality and Induction
time frame: Weekly during treatment, at third month and at 6 months after last administration of Mylotarg
Capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation
time frame: One month before transplant, expected at 9 months after end of treatment.
Relapse after 6 months
time frame: 6 months from complete remission
Survival after 6 months
time frame: 6 months after complete remission

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

Inclusion Criteria: 1. Patients with primary or "de novo" AML, different than promyelocytic or M3 subtype. 2. Age 18 to 70 years. 3. Written informed consent form Exclusion Criteria: 1. Acute leukemia appeared after a myeloproliferative process or a myelodysplastic syndrome longer than 6 months, AML arising after another cured malignant disease (e.g. Hodgkin's disease), and secondary AML treated with alkylating agents or radiation. 2. Acute promyelocytic leukemia. 3. Relevant history of liver disease. Significant impaired liver function (bilirubin, AST or ALT ≥ 2.5 times the normal value) not attributable to leukemic infiltration. 4. Patients with prior heart failure. 5. Symptomatic chronic respiratory failure. 6. Positive serology for HIV, hepatitis C virus or its surface antigen. 7. Estimated life expectancy less than 3 months, despite treatment. 8. Pregnancy or breastfeeding at the time of inclusion in the study.

Additional Information

Official title Treatment of de Novo Acute Myeloid Leukemia With the Combination of Idarubicin, Cytarabine, and Gemtuzumab Ozogamicin (Mylotarg ®), Associated or Not Priming With G-CSF. Prospective Study of Efficacy and Toxicity
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias.