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Trial record 50 of 50 for:    "Essential Thrombocythemia" | "Anti-Infective Agents"

Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

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ClinicalTrials.gov Identifier: NCT02084563
Recruitment Status : Completed
First Posted : March 12, 2014
Last Update Posted : November 8, 2016
Sponsor:
Information provided by (Responsible Party):
Fabio Pires de Souza Santos, 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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Myeloproliferative Neoplasms Myelodysplastic Syndromes Myeloproliferative/Myelodysplastic Neoplasm Drug: Induction Chemotherapy Drug: Consolidation Chemotherapy Drug: Autologous Stem Cell Transplantation Drug: Allogeneic Stem Cell Transplantation Drug: Low Dose Cytarabine Drug: Decitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 455 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Study Start Date : October 2012
Actual Primary Completion Date : December 2014
Actual Study Completion Date : November 2016


Arm Intervention/treatment
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.
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
Other Names:
  • 7+3
  • Ara-C
  • Daunorubicin
  • Anthracycline
  • 3+7

Drug: 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

Other Names:
  • Ara-C
  • Cytarabine

Drug: 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
Other Names:
  • ASCT
  • Autologous Bone Marrow Transplantation
  • ABMT

Drug: 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
Other Names:
  • AlloSCT
  • Allogeneic Bone Marrow 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.

Drug: 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)
Other Names:
  • Low dose ara-C
  • LDAC

Drug: 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)
Other Names:
  • 2-aza-5´-deoxycytidine
  • Dacogen
  • DAC

No Intervention: Chronic Myeloid Disorders

Patients with Chronic Myeloid Disorders:

  • Myeloproliferative Neoplasms
  • Myelodysplastic Syndromes
  • Myeloproliferative/Myelodysplastic Neoplasms



Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Overall survival [ Time Frame: 5 years ]
    Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms

  2. Response rate [ Time Frame: 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)

  3. Disease Free Survival [ Time Frame: 5 years ]
    Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy

  4. Cumulative incidence of relapse and non-relapse mortality [ Time Frame: 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

  5. Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 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

  6. Cumulative Incidence of Transformation to Acute Myeloid Leukemia [ Time Frame: 5 years ]
    Evaluate 5-years incidence of transformation to Acute Myeloid Leukemia in patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02084563


Locations
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Brazil
Hospital Israelita Albert Einstein
Sao Paulo, SP, Brazil, 05651901
Sponsors and Collaborators
Hospital Israelita Albert Einstein
Investigators
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Study Director: Fabio P Santos, MD Hospital Israelita Albert Einstein
Study Chair: Nelson Hamerschlak, MD, PhD Hospital Israelita Albert Einstein

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Responsible Party: Fabio Pires de Souza Santos, MD, Hospital Israelita Albert Einstein
ClinicalTrials.gov Identifier: NCT02084563     History of Changes
Other Study ID Numbers: LMA Brasil
11/1714 ( Other Identifier: HIAE CEP )
First Posted: March 12, 2014    Key Record Dates
Last Update Posted: November 8, 2016
Last Verified: November 2016
Keywords provided by Fabio Pires de Souza Santos, Hospital Israelita Albert Einstein:
Essential Thrombocythemia (ET)
Acute Myeloid Leukemia
Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Myeloproliferative/Myelodysplastic Neoplasm
Leukemia
MDS
MPN
AML
Chronic myelomonocytic leukemia (CMML)
Polycythemia Vera (PV)
Myelofibrosis (MF)
Additional relevant MeSH terms:
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Anti-Infective Agents
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Myelodysplastic Syndromes
Myeloproliferative Disorders
Syndrome
Neoplasms
Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Cytarabine
Decitabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors