Evaluation of the Incidence and Prognostic Impact of Molecular and Genetic Abnormalities in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms
Overview
- Phase
- Phase 2
- Intervention
- Induction Chemotherapy
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- Hospital Israelita Albert Einstein
- Enrollment
- 455
- Locations
- 1
- Primary Endpoint
- Prevalence of molecular and cytogenetic abnormalities
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
Fabio Pires de Souza Santos
MD
Hospital Israelita Albert Einstein
Eligibility Criteria
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
Arms & Interventions
AML-Intensive 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.
Intervention: Induction Chemotherapy
AML-Intensive 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.
Intervention: Consolidation Chemotherapy
AML-Intensive 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.
Intervention: Autologous Stem Cell Transplantation
AML-Intensive 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.
Intervention: Allogeneic Stem Cell Transplantation
AML-Non-intensive chemotherapy
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.
Intervention: Low Dose Cytarabine
AML-Non-intensive chemotherapy
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.
Intervention: Decitabine
Outcomes
Primary Outcomes
Prevalence of molecular and cytogenetic abnormalities
Time Frame: 2 years
As assessed by results of molecular and cytogenetic tests and frequency in the population studied
Secondary Outcomes
- Number of participants with adverse events as a measure of safety and tolerability(1 year)
- Response rate(1 month)
- Cumulative Incidence of Transformation to Acute Myeloid Leukemia(5 years)
- Overall survival(5 years)
- Cumulative incidence of relapse and non-relapse mortality(5 years)
- Disease Free Survival(5 years)