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

NCT ID: NCT01698879

Last Updated: 2021-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2016-09-26

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.

Conditions

Novo Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single arm, three cohorts

Idarubicin, cytarabine, Mylotarg.

Group Type: EXPERIMENTAL

Mylotarg

Intervention Type: DRUG

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.

Interventions

Mylotarg

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 Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jordi Sierra, MD

Role: STUDY_CHAIR

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Locations

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Clinic Barcelona

Barcelona, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Countries

Spain

Other Identifiers

2007-006295-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ICOG-07

Identifier Type: -

Identifier Source: org_study_id