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Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

Primary Purpose

Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Induction Chemotherapy
Consolidation Chemotherapy
Autologous Stem Cell Transplantation
Allogeneic Stem Cell Transplantation
Low Dose Cytarabine
Decitabine
Sponsored by
Hospital Israelita Albert Einstein
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Acute Myeloid Leukemia focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital Israelita Albert Einstein

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Other

No Intervention

Arm Label

AML-Intensive Chemotherapy

AML-Non-intensive chemotherapy

Chronic Myeloid Disorders

Arm 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.

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.

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival
Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms
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)
Disease Free Survival
Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy
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
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
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

Full Information

First Posted
January 2, 2013
Last Updated
November 7, 2016
Sponsor
Hospital Israelita Albert Einstein
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1. Study Identification

Unique Protocol Identification Number
NCT02084563
Brief Title
Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms
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 Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hospital Israelita Albert Einstein

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
455 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AML-Intensive Chemotherapy
Arm Type
Other
Arm 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.
Arm Title
AML-Non-intensive chemotherapy
Arm Type
Other
Arm 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.
Arm Title
Chronic Myeloid Disorders
Arm Type
No Intervention
Arm Description
Patients with Chronic Myeloid Disorders: Myeloproliferative Neoplasms Myelodysplastic Syndromes Myeloproliferative/Myelodysplastic Neoplasms
Intervention Type
Drug
Intervention Name(s)
Induction Chemotherapy
Other Intervention Name(s)
7+3, Ara-C, Daunorubicin, Anthracycline, 3+7
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Consolidation Chemotherapy
Other Intervention Name(s)
Ara-C, Cytarabine
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Autologous Stem Cell Transplantation
Other Intervention Name(s)
ASCT, Autologous Bone Marrow Transplantation, ABMT
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Allogeneic Stem Cell Transplantation
Other Intervention Name(s)
AlloSCT, Allogeneic Bone Marrow Transplantation
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Low Dose Cytarabine
Other Intervention Name(s)
Low dose ara-C, LDAC
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
2-aza-5´-deoxycytidine, Dacogen, DAC
Intervention Description
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)
Primary Outcome Measure Information:
Title
Prevalence of molecular and cytogenetic abnormalities
Description
As assessed by results of molecular and cytogenetic tests and frequency in the population studied
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall survival
Description
Evaluation of 5-years overall survival in patients with Acute Myeloid Leukemia, Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms
Time Frame
5 years
Title
Response rate
Description
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)
Time Frame
1 month
Title
Disease Free Survival
Description
Evaluate rate of 5-years disease-free survival in patients with Acute Myeloid Leukemia who enter complete remission after induction chemotherapy
Time Frame
5 years
Title
Cumulative incidence of relapse and non-relapse mortality
Description
Evaluate 5-years cumulative incidence of relapse and non-relapse mortality in patients with Acute Myeloid Leukemia who achieve complete remission following induction chemotherapy
Time Frame
5 years
Title
Number of participants with adverse events as a measure of safety and tolerability
Description
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
Time Frame
1 year
Title
Cumulative Incidence of Transformation to Acute Myeloid Leukemia
Description
Evaluate 5-years incidence of transformation to Acute Myeloid Leukemia in patients with Myeloproliferative Neoplasms, Myelodysplastic Syndromes and Myeloproliferative/Myelodysplastic Neoplasms
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fabio P Santos, MD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Nelson Hamerschlak, MD, PhD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Israelita Albert Einstein
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
05651901
Country
Brazil

12. IPD Sharing Statement

Learn more about this trial

Study of Molecular and Genetic Abnormalities in Patients With Myeloid Neoplasms

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