Clinical trial NCT01698879: Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Novo Acute Myeloid Leukemia
Lead sponsor: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Sponsor class: OTHER
First posted: 2012-10-03
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Complete Remission of the Disease
timeFrame: 28 days after chemotherapy
Secondary outcomes:
measure: Secondary Toxicity to Mylotarg(R)
timeFrame: Baseline, weekly during treatment and at month 3 and month 6 after first induction.
measure: Mortality at Induction
timeFrame: Weekly during treatment, at third month and at 6 months after last administration of Mylotarg
measure: Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED
timeFrame: One month before transplant, expected at 9 months after end of treatment.
measure: Relapse After 6 Months
timeFrame: 6 months from complete remission
measure: Survival After 6 Months
timeFrame: 6 months after complete remission
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Jordi Sierra, MD
role: STUDY_CHAIR
References: