Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

Hospital Israelita Albert Einstein

Status and phase: Completed; Phase 2

Conditions: Myeloproliferative Neoplasms; Myeloproliferative/Myelodysplastic Neoplasm; Myelodysplastic Syndromes; Acute Myeloid Leukemia

Treatments: Drug: Autologous Stem Cell Transplantation; Drug: Decitabine; Drug: Consolidation Chemotherapy; Drug: Allogeneic Stem Cell Transplantation; Drug: Induction Chemotherapy; Drug: Low Dose Cytarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT02084563

LMA Brasil

11/1714 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 455 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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)

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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455 participants in 3 patient groups

AML-Intensive Chemotherapy

Other group

Description:

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.

Treatment:

Drug: Allogeneic Stem Cell Transplantation

Drug: Consolidation Chemotherapy

Drug: Autologous Stem Cell Transplantation

Drug: Induction Chemotherapy

AML-Non-intensive chemotherapy

Other group

Description:

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.

Treatment:

Drug: Decitabine

Drug: Low Dose Cytarabine

Chronic Myeloid Disorders

No Intervention group

Description:

Patients with Chronic Myeloid Disorders: * Myeloproliferative Neoplasms * Myelodysplastic Syndromes * Myeloproliferative/Myelodysplastic Neoplasms