Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment
Condition: Novo Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Mylotarg
Intervention description: 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.
Intervention MeSH terms: Gemtuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

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.