Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

Phase 2CompletedNCT02084563

Hospital Israelita Albert Einstein455 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

455

Conditions

Acute Myeloid Leukemia Myeloproliferative Neoplasms Myelodysplastic Syndromes Myeloproliferative/Myelodysplastic Neoplasm

Interventions

Induction ChemotherapyDRUG

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 ChemotherapyDRUG

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 TransplantationDRUG

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 TransplantationDRUG

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

Low Dose CytarabineDRUG

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)

DecitabineDRUG

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)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Prevalence of molecular and cytogenetic abnormalities

As assessed by results of molecular and cytogenetic tests and frequency in the population studied

Time frame: 2 years

Secondary Outcomes

Overall survival

Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms

Time frame: 5 years

Response rate

Evaluate complete remission (CR) rate at 1 month for patients with Acute Myeloid Leukemia who received induction chemotherapy. Complete remission was defined by the presence of \< 5% blasts in the bone marrow (BM) with \> 1 x 10\^9/L neutrophils and \>100x10\^9/L platelets in the peripheral blood (PB)

Time frame: 1 month

Disease Free Survival

Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy

Time frame: 5 years

Cumulative incidence of relapse and non-relapse mortality

Evaluate 5-years cumulative incidence of relapse and non-relapse mortality in patients with Acute Myeloid Leukemia who achieve complete remission following induction chemotherapy

Time frame: 5 years

Number of participants with adverse events as a measure of safety and tolerability

Evaluate hematological and non-hematological toxicity in patients with Acute Myeloid Leukemia treated according to the protocol. Toxicity will be graded as per the National Cancer Institute Common Toxicity Criteria for Adverse Events v4.0.3

Time frame: 1 year

Cumulative Incidence of Transformation to Acute Myeloid Leukemia

Evaluate 5-years incidence of transformation to Acute Myeloid Leukemia in patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms

Time frame: 5 years

Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes