Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

NCT02084563 | Completed Phase 2 DMC

• 2 other identifiers: LMA Brasil11/1714
• Study Type: interventional
• Target: 455
• Locations: 1 country
• Sites: 1

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.

Conditions

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

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)

Outcome Measures

Primary Outcomes (1)

• Prevalence of molecular and cytogenetic abnormalities

  As assessed by results of molecular and cytogenetic tests and frequency in the population studied

  2 years

Secondary Outcomes (6)

• Overall survival

  5 years

• Response rate

  1 month

• Disease Free Survival

  5 years

• Cumulative incidence of relapse and non-relapse mortality

  5 years

• Number of participants with adverse events as a measure of safety and tolerability

  1 year

Study Arms (3)

AML-Intensive Chemotherapy

OTHER

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.

Drug: Induction Chemotherapy; Drug: Consolidation Chemotherapy; Drug: Autologous Stem Cell Transplantation; Drug: Allogeneic Stem Cell Transplantation

AML-Non-intensive chemotherapy

OTHER

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.

Drug: Low Dose Cytarabine; Drug: Decitabine

Chronic Myeloid Disorders

NO INTERVENTION

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

Interventions

Induction Chemotherapy DRUG

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

Also known as: 7+3, Ara-C, Daunorubicin, Anthracycline, 3+7

AML-Intensive Chemotherapy

Consolidation Chemotherapy DRUG

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

Also known as: Ara-C, Cytarabine

AML-Intensive Chemotherapy

Autologous Stem Cell Transplantation DRUG

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

Also known as: ASCT, Autologous Bone Marrow Transplantation, ABMT

AML-Intensive Chemotherapy

Allogeneic Stem Cell Transplantation DRUG

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

Also known as: AlloSCT, Allogeneic Bone Marrow Transplantation

AML-Intensive Chemotherapy

Low Dose Cytarabine DRUG

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)

Also known as: Low dose ara-C, LDAC

AML-Non-intensive chemotherapy

Decitabine DRUG

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)

Also known as: 2-aza-5´-deoxycytidine, Dacogen, DAC

AML-Non-intensive chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)
• Acute myeloid leukemia with RARA translocations (APL, acute promyelocytic leukemia)

Sponsors & Collaborators

• Hospital Israelita Albert Einstein: lead

Study Sites (1)

Hospital Israelita Albert Einstein

São Paulo, São Paulo, 05651901, Brazil

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Leukemia; Leukemia, Myelomonocytic, Chronic; Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

Induction Chemotherapy; Cytarabine; Daunorubicin; Anthracyclines; Consolidation Chemotherapy; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics; Remission Induction; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Azacitidine; Aza Compounds; Ribonucleosides

Study Officials

• Fabio P Santos, MD

  Hospital Israelita Albert Einstein

  STUDY DIRECTOR

• Nelson Hamerschlak, MD, PhD

  Hospital Israelita Albert Einstein

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 2, 2013
• First Posted: March 12, 2014
• Study Start: October 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: November 1, 2016
• Last Updated: November 8, 2016

Record last verified: 2016-11

Locations

BR (1)