Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

Acute Myeloid Leukemia Clinical Trial

Official title:

Evaluation of the Incidence and Prognostic Impact of Molecular and Genetic Abnormalities in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome and Myeloproliferative Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02084563
• Other study ID #: LMA Brasil
• Secondary ID: 11/1714
• Status: Completed
• Phase: Phase 2
• First received: January 2, 2013
• Last updated: November 7, 2016
• Start date: October 2012
• Est. completion date: November 2016

Study information

• Verified date: November 2016
• Source: Hospital Israelita Albert Einstein
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 455
• Est. completion date: November 2016
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Myeloproliferative Neoplasms
• Myeloproliferative/Myelodysplastic Neoplasm
• Neoplasms
• Preleukemia
• Syndrome

Intervention

Drug:
• Induction 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
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 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
• Allogeneic 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
• Low Dose Cytarabine
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)
• Decitabine
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)

Locations

Country	Name	City	State
Brazil	Hospital Israelita Albert Einstein	Sao Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of molecular and cytogenetic abnormalities	As assessed by results of molecular and cytogenetic tests and frequency in the population studied	2 years	No
Secondary	Overall survival	Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms	5 years	No
Secondary	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)	1 month	No
Secondary	Disease Free Survival	Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy	5 years	No
Secondary	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	5 years	No
Secondary	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	1 year	Yes
Secondary	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	5 years	No