Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Myeloproliferative/Myelodysplastic Neoplasm
Conditions
Keywords
Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes, Myeloproliferative/Myelodysplastic Neoplasm, Leukemia, MDS, MPN, AML, Chronic myelomonocytic leukemia (CMML), Polycythemia Vera (PV), Essential Thrombocythemia (ET), Myelofibrosis (MF)
Brief 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.
Interventions
DRUGInduction Chemotherapy
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 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
DRUGAutologous Stem Cell Transplantation
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
DRUGAllogeneic Stem Cell Transplantation
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
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)
DRUGDecitabine
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)
Sponsors
Hospital Israelita Albert Einstein
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of molecular and cytogenetic abnormalities | 2 years | As assessed by results of molecular and cytogenetic tests and frequency in the population studied |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response rate | 1 month | 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) |
| Disease Free Survival | 5 years | Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy |
| Overall survival | 5 years | Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms |
| Number of participants with adverse events as a measure of safety and tolerability | 1 year | 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 |
| Cumulative Incidence of Transformation to Acute Myeloid Leukemia | 5 years | Evaluate 5-years incidence of transformation to Acute Myeloid Leukemia in patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms |
| Cumulative incidence of relapse and non-relapse mortality | 5 years | Evaluate 5-years cumulative incidence of relapse and non-relapse mortality in patients with Acute Myeloid Leukemia who achieve complete remission following induction chemotherapy |
Countries
Brazil
Outcome results
None listed