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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01698879
Recruitment Status : Active, not recruiting
First Posted : October 3, 2012
Last Update Posted : August 11, 2016
Information provided by (Responsible Party):
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

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.

Condition or disease Intervention/treatment Phase
Novo Acute Myeloid Leukemia Drug: Mylotarg Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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 Start Date : October 2009
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : December 2016

Arm Intervention/treatment
Experimental: Single arm, two cohorts
Idarubicin, cytarabine, Mylotarg, G-CSF.
Drug: Mylotarg

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 Outcome Measures :
  1. Complete Remission of the Disease [ Time Frame: 28 days after chemotherapy ]
    Bone marrow normocellular or slightly hypocellular with proportion of blasts <5%, including the erythroid cell count (and including promonocytes in case of M5), no Auer rods, no extramedullary leukemia, neutrophils and platelets rising. The persistence of minimal residual disease in immunophenotypic study will not invalidate the standard cytogenetic complete remission

Secondary Outcome Measures :
  1. Secondary Toxicity to Mylotarg(R) [ Time Frame: Baseline, weekly during treatment and at month 3 and month 6 after first induction. ]
    Hematological toxicity, hepatic and gastrointestinal toxicity, fever and infections, pulmonary complications, duration of hospitalization

  2. Mortality and Induction [ Time Frame: Weekly during treatment, at third month and at 6 months after last administration of Mylotarg ]
    all deaths occurring after the first administration of MylotargTM until the time of transplantation with no leukemic relapse has occurred, and all deaths in the 6 first months after administration of the second dose of MylotargTM with no leukemic relapse occurred.

  3. Capacity to obtain hematopoietic progenitor cells (HPC) for autotransplantation [ Time Frame: One month before transplant, expected at 9 months after end of treatment. ]
  4. Relapse after 6 months [ Time Frame: 6 months from complete remission ]
    Rate of patients that have relapse after 6 months of obtained complete remission.

  5. Survival after 6 months [ Time Frame: 6 months after complete remission ]
    rate of patients alive within 6 months of obtained complete remission

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01698879

Hospital Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08025
Hospital Clinic Barcelona
Barcelona, Spain, 08036
Hospital Clinico Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Clínico Universitario de Valencia
Valencia, Spain, 496010
Sponsors and Collaborators
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Study Chair: Jordi Sierra, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Responsible Party: Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias Identifier: NCT01698879     History of Changes
Other Study ID Numbers: ICOG-07
2007-006295-11 ( EudraCT Number )
First Posted: October 3, 2012    Key Record Dates
Last Update Posted: August 11, 2016
Last Verified: August 2016

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors