Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment
|ClinicalTrials.gov Identifier: NCT01698879|
Recruitment Status : Active, not recruiting
First Posted : October 3, 2012
Last Update Posted : August 11, 2016
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)|
|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|
Experimental: Single arm, two cohorts
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.
- 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 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
- 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.
- 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 ]Rate of patients that have relapse after 6 months of obtained complete remission.
- Survival after 6 months [ Time Frame: 6 months after complete remission ]rate of patients alive within 6 months of obtained complete remission
Please refer to this study by its ClinicalTrials.gov 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|
|Study Chair:||Jordi Sierra, MD||Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau|