Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms
- Conditions
- Myeloproliferative NeoplasmsMyelodysplastic SyndromesAcute Myeloid LeukemiaMyeloproliferative/Myelodysplastic Neoplasm
- Interventions
- Drug: Induction ChemotherapyDrug: Consolidation ChemotherapyDrug: Autologous Stem Cell TransplantationDrug: Allogeneic Stem Cell Transplantation
- Registration Number
- NCT02084563
- Lead Sponsor
- Hospital Israelita Albert Einstein
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 455
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AML-Non-intensive chemotherapy Low Dose Cytarabine 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. AML-Intensive Chemotherapy Induction Chemotherapy 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. AML-Intensive Chemotherapy Autologous Stem Cell Transplantation 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. AML-Intensive Chemotherapy Allogeneic Stem Cell Transplantation 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. AML-Intensive Chemotherapy Consolidation Chemotherapy 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. AML-Non-intensive chemotherapy Decitabine 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.
- Primary Outcome Measures
Name Time Method Prevalence of molecular and cytogenetic abnormalities 2 years As assessed by results of molecular and cytogenetic tests and frequency in the population studied
- Secondary Outcome Measures
Name Time Method 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)
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
Overall survival 5 years Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, 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
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
Trial Locations
- Locations (1)
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, SP, Brazil