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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2012 by Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
ClinicalTrials.gov Identifier:
NCT01698879
First received: July 23, 2012
Last updated: October 1, 2012
Last verified: October 2012

July 23, 2012
October 1, 2012
October 2009
December 2012   (final data collection date for primary outcome measure)
Complete Remission of the Disease [ Time Frame: 28 days after chemotherapy ] [ Designated as safety issue: No ]
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
Same as current
Complete list of historical versions of study NCT01698879 on ClinicalTrials.gov Archive Site
  • Secondary Toxicity to Mylotarg(R) [ Time Frame: Baseline, weekly during treatment and at month 3 and month 6 after first induction. ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: No ]
  • Relapse after 6 months [ Time Frame: 6 months from complete remission ] [ Designated as safety issue: No ]
    Rate of patients that have relapse after 6 months of obtained complete remission.
  • Survival after 6 months [ Time Frame: 6 months after complete remission ] [ Designated as safety issue: No ]
    rate of patients alive within 6 months of obtained complete remission
Same as current
Not Provided
Not Provided
 
Prospective Study of Mylotarg and G-CSF in Acute Myeloid Leukemia Treatment
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

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Novo Acute Myeloid Leukemia
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.

Experimental: Single arm, two cohorts
Idarubicin, cytarabine, Mylotarg, G-CSF.
Intervention: Drug: Mylotarg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
February 2013
December 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01698879
ICOG-07, 2007-006295-11
No
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
Not Provided
Study Chair: Jordi Sierra, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Grupo Cooperativo de Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias
October 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP