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

NCT01698879 | Completed Phase 2 Results

• 2 other identifiers: ICOG-072007-006295-11
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 6

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

Outcome Measures

Primary Outcomes (1)

• Complete Remission of the Disease

  Rate of patients that have obtained complete remission. Complete remission is defined as, 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.

  28 days after chemotherapy

Secondary Outcomes (5)

• Secondary Toxicity to Mylotarg(R)

  Baseline, weekly during treatment and at month 3 and month 6 after first induction.

• Mortality at Induction

  Weekly during treatment, at third month and at 6 months after last administration of Mylotarg

• Capacity to Obtain Hematopoietic Progenitor Cells (HPC) for Autotransplantation - DATA NOT COLLECTED

  One month before transplant, expected at 9 months after end of treatment.

• Relapse After 6 Months

  6 months from complete remission

• Survival After 6 Months

  6 months after complete remission

Study Arms (1)

Single arm, three cohorts

EXPERIMENTAL

Idarubicin, cytarabine, Mylotarg.

Drug: Mylotarg

Interventions

Mylotarg 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.

Single arm, three cohorts

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with primary or "de novo" AML, different than promyelocytic or M3 subtype.
• Age 18 to 70 years.
• Written informed consent form

You may not qualify if:

• 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.
• Acute promyelocytic leukemia.
• Relevant history of liver disease. Significant impaired liver function (bilirubin, AST or ALT ≥ 2.5 times the normal value) not attributable to leukemic infiltration.
• Patients with prior heart failure.
• Symptomatic chronic respiratory failure.
• Positive serology for HIV, hepatitis C virus or its surface antigen.
• Estimated life expectancy less than 3 months, despite treatment.

Sponsors & Collaborators

• Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias: lead

Study Sites (6)

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 496010, Spain

Location

MeSH Terms

Interventions

Gemtuzumab

Intervention Hierarchy (Ancestors)

Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Jordi Sierra
• Organization: CETLAM

jsierra@santpau.cat

+34 93 434 44 12

Study Officials

• Jordi Sierra, MD

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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: October 3, 2012
• Study Start: October 1, 2009
• Primary Completion: September 14, 2016
• Study Completion: September 26, 2016
• Last Updated: January 27, 2021
• Results First Posted: January 27, 2021

Record last verified: 2021-01

Locations

ES (6)