Overview

This trial has been completed.

Conditions acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes, myeloproliferative/myelodysplastic neoplasm
Treatments induction chemotherapy, consolidation chemotherapy, autologous stem cell transplantation, allogeneic stem cell transplantation, low dose cytarabine, decitabine
Phase phase 2
Sponsor Hospital Israelita Albert Einstein
Start date October 2012
End date December 2014
Trial size 455 participants
Trial identifier NCT02084563, 11/1714, LMA Brasil

Summary

The objective of this study is to describe the prevalence and prognostic impact of the most common genetic abnormalities in patients with Myeloid Neoplasms, including Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPN), Myelodysplastic Syndromes (MDS) and Myeloproliferative/Myelodysplastic Neoplasms. Patients will have samples of blood and/or bone marrow collected and sent to Hospital Israelita Albert Einstein for analysis and storage.

Patients with a diagnosis of Acute Myeloid Leukemia will be treated according to an uniform protocol.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose basic science
Arm
(Other)
Patients with Acute Myeloid Leukemia fit for intensive chemotherapy Patients will receive Induction Chemotherapy, and CR will be evaluated after 28 days. Patients who achieve CR post-induction chemotherapy will receive post-remission therapy according to risk: Low risk patients: Consolidation chemotherapy or Autologous stem cell transplantation Intermediate and high-risk patients: Allogeneic stem cell transplantation Patients who do not achieve CR may receive one second induction cycle, and if CR is achieved may proceed to post-remission therapy as per above. Patients who do not achieve CR after two cycles of induction will be deemed refractory and removed from the study.
induction chemotherapy 7+3
Induction chemotherapy for patients with AML eligible for intensive chemotherapy: Cytarabine 200 mg/m2 IV continuous infusion days 1-7 Daunorubicin 90 mg/m2 intravenous piggyback days 1-3
consolidation chemotherapy Ara-C
Consolidation chemotherapy for patients eligible for intensive chemotherapy with low-risk AML or patients with intermediate-/high-risk AML who do not have matched donors: -Cytarabine 1.5 g/m2 IV in 3 hours days 1, 3 and 5 for 3 cycles
autologous stem cell transplantation ASCT
Autologous Stem Cell Transplantation for consolidation of patients eligible for intensive chemotherapy with low-risk AML or patients with intermediate-/high-risk AML who do not have matched donors: Busulfan 1 mg/Kg PO q6h or 130 mg/m2 IV once daily days -7 to -4 Cyclophosphamide 60 mg/Kg IV once daily days -3 and -2
allogeneic stem cell transplantation AlloSCT
Allogeneic Stem Cell Transplantation for consolidation of patients eligible for intensive chemotherapy with intermediate-/high-risk AML Conditioning regimen: Busulfan 1 mg/Kg PO q6h or 130 mg/m2 IV once daily days -7 to -4 Cyclophosphamide 60 mg/Kg IV once daily days -3 and -2 or Fludarabine 40 mg/m2 IV once daily days -7 to -4
(Other)
Patients with acute myeloid leukemia not fit for intensive chemotherapy Patients will receive induction chemotherapy with either low dose cytarabine or decitabine. Assignment to each drug will depend on drug availability and physician discretion. No randomization will be done between the drugs. Cycles will be repeated every 28 days. Patients who achieve CR will continue to post-consolidation therapy with either cytarabine or decitabine, based on the induction therapy received. Patients will receive a maximum of 4 cycles until achieving CR, if no response is seen after 4 cycles patients will be deemed refractory.
low dose cytarabine Low dose ara-C
Chemotherapy for patients with AML who are not fit for intensive chemotherapy: Cytarabine 60 mg/m2 subcutaneous (SQ) bid days 1-5 (until CR or maximum 4 cycles) Cytarabine 40 mg/m2 SQ bid days 1-5 (after CR, until a maximum of 3 years of therapy or relapse, whichever comes first)
decitabine 2-aza-5´-deoxycytidine
Chemotherapy for patients with AML who are not fit for intensive chemotherapy: Decitabine 20 mg/m2 IV once daily days 1-10 (until CR or maximum 4 cycles) Decitabine 20 mg/m2 IV once daily days 1-5 (after CR, until a maximum of 3 years of therapy or relapse, whichever comes first)
(No Intervention)
Patients with Chronic Myeloid Disorders: Myeloproliferative Neoplasms Myelodysplastic Syndromes Myeloproliferative/Myelodysplastic Neoplasms

Primary Outcomes

Measure
Prevalence of molecular and cytogenetic abnormalities
time frame: 2 years

Secondary Outcomes

Measure
Overall survival
time frame: 5 years
Response rate
time frame: 1 month
Disease Free Survival
time frame: 5 years
Cumulative incidence of relapse and non-relapse mortality
time frame: 5 years
Number of participants with adverse events as a measure of safety and tolerability
time frame: 1 year
Cumulative Incidence of Transformation to Acute Myeloid Leukemia
time frame: 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Acute Myeloid Leukemia-Intensive Chemotherapy Inclusion Criteria: - Diagnosis of AML according to WHO criteria - Age greater than 18 years - Performance status (ECOG) between 0-2 - Adequate liver and kidney function - Signed Informed Consent form - No prior therapy for AML, except use of hydroxyurea for control of elevated white blood cell counts - Adequate contraception for fertile men and women - Eligible for intensive chemotherapy (as judged by the treating physician) Exclusion Criteria: - Acute myeloid leukemia with retinoic acid receptor alpha (RARA) translocations (APL, acute promyelocytic leukemia) - Pregnant women - HIV-positivity - New York Heart Association class III and IV congestive heart failure - Patient refuses to use adequate contraception - History of hypersensibility to any of the used chemotherapy drugs - Patient refuses to sign informed consent form Acute Myeloid Leukemia-Non-Intensive Chemotherapy Inclusion Criteria: - Diagnosis of AML according to WHO criteria - Age greater than 18 years - Signed Informed Consent form - No prior therapy for AML, except use of hydroxyurea for control of elevated white blood cell counts - Adequate contraception for fertile men and women - Non-eligible for intensive chemotherapy (as judged by the treating physician) Exclusion Criteria: - Acute myeloid leukemia with RARA translocations (APL, acute promyelocytic leukemia) - Pregnant women - HIV-positivity - Patient refuses to use adequate contraception - History of hypersensibility to any of the used chemotherapy drugs - Patient refuses to sign informed consent form Chronic Myeloid Disorders: Inclusion Criteria: - Diagnosis of Myeloproliferative Neoplasm or Myelodysplastic Syndrome or Myeloproliferative/Myelodysplastic Neoplasm according to WHO criteria - Age greater than 18 years - Signed Informed Consent form Exclusion Criteria: - Patient refuses to sign informed consent form

Additional Information

Official title Evaluation of the Incidence and Prognostic Impact of Molecular and Genetic Abnormalities in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hospital Israelita Albert Einstein.