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Azacitidine in Treating Patients With Myelofibrosis

Primary Purpose

Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
azacitidine
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring primary myelofibrosis, polycythemia vera, essential thrombocythemia, secondary myelofibrosis

Eligibility Criteria

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed myelofibrosis with myeloid metaplasia (MMM), including any of the following subtypes:

    • Agnogenic myeloid metaplasia
    • Post-polycythemic myeloid metaplasia
    • Post-thrombocythemic myeloid metaplasia

  • Evaluable and symptomatic disease, defined as 1 of the following:

    • Anemia (hemoglobin < 10 g/dL or erythrocyte transfusion-dependent, requiring 1 transfusion ≤ 8 weeks)
    • Treatment required* for symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) NOTE: *Subjective but painful enough to mandate intervention

  • Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard cytogenetics (by peripheral blood or marrow)

    - Previous demonstration of a lack of this translocation (at any point) is sufficient

  • No advanced malignant hepatic tumors

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,000/mm³
  • Platelet count ≥ 50,000/mm³
  • Creatinine ≤ 2.0 mg/dL
  • Total bilirubin ≤ 2.0 mg/dL OR direct bilirubin ≤ 2.0 mg/dL if total bilirubin elevated (unless attributed to underlying disease)
  • AST and ALT ≤ 2 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No baseline peripheral or autonomic neuropathy ≥ grade 2
  • No condition, including the presence of laboratory abnormalities, that would preclude study compliance
  • No hypersensitivity to mannitol or azacitidine
  • Not incarcerated in a municipality (i.e., county, state, or federal prison)

PRIOR CONCURRENT THERAPY:

  • At least 14 days since prior chemotherapy, including interferon alfa, anagrelide, or other myelosuppressive agents
  • At least 14 days since prior systemic corticosteroids
  • At least 14 days since prior investigational agents

Sites / Locations

  • Mayo Clinic in Arizona
  • Mayo Clinic

Outcomes

Primary Outcome Measures

Patients With Confirmed Response (Complete Remission or Partial Remission on 2 Consecutive Evaluation at Least 4 Weeks Apart) During the First 4 Months of Treatment
Response Definitions: Completion Remission (CR):complete resolution of disease-related symptoms, ultrasound-documented resolution of hepastosplenomegaly, normalization of the peripheral blood count, white cell differential, and smear, normalization of bone marrow histology including disappearance of fibrosis and osteosclerosis. Residual cytogenetic abnormalities are allowed. Partial Remission (PR): a major response in any baseline applicable criteria (except constitutional symptoms) without progression in any other category.

Secondary Outcome Measures

Overall Survival (OS)
OS was defined as the time from registration to death due to any cause or time from registration to 3 years after registration if patient is still alive.
Time to Progression
Time to progression was defined as the time from registration to progression of disease. Those who die without documentation of disease progression will be considered to have had disease progression at the time of their death unless documented evidence clearly indicates no progression has occured.
Number of Participants With Treatment Related Adverse Events
Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE. Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE

Full Information

First Posted
September 26, 2006
Last Updated
April 19, 2011
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00381693
Brief Title
Azacitidine in Treating Patients With Myelofibrosis
Official Title
Phase II Study of Azacitidine in Myelofibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Terminated
Why Stopped
Due to lack of accrual and trial has demonstrated too little clinical benefit
Study Start Date
August 2006 (undefined)
Primary Completion Date
March 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of abnormal cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well azacitidine works in treating patients with myelofibrosis.
Detailed Description
OBJECTIVES: Primary Determine the efficacy of azacitidine in patients with myelofibrosis (MF) with myeloid metaplasia. Evaluate the safety of azacitidine in these patients. Secondary Evaluate pertinent biologic characteristics of MF before and during therapy with azacitidine. Assess the effects of study treatment on constitutional symptoms in these patients. Estimate time to event distributions for overall survival and progression. OUTLINE: Patients receive azacitidine subcutaneously once daily on days 1-5. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 3 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Keywords
primary myelofibrosis, polycythemia vera, essential thrombocythemia, secondary myelofibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
azacitidine
Primary Outcome Measure Information:
Title
Patients With Confirmed Response (Complete Remission or Partial Remission on 2 Consecutive Evaluation at Least 4 Weeks Apart) During the First 4 Months of Treatment
Description
Response Definitions: Completion Remission (CR):complete resolution of disease-related symptoms, ultrasound-documented resolution of hepastosplenomegaly, normalization of the peripheral blood count, white cell differential, and smear, normalization of bone marrow histology including disappearance of fibrosis and osteosclerosis. Residual cytogenetic abnormalities are allowed. Partial Remission (PR): a major response in any baseline applicable criteria (except constitutional symptoms) without progression in any other category.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
OS was defined as the time from registration to death due to any cause or time from registration to 3 years after registration if patient is still alive.
Time Frame
From date of registration until death or 3 years after registration if patient is still alive
Title
Time to Progression
Description
Time to progression was defined as the time from registration to progression of disease. Those who die without documentation of disease progression will be considered to have had disease progression at the time of their death unless documented evidence clearly indicates no progression has occured.
Time Frame
up to 3 years
Title
Number of Participants With Treatment Related Adverse Events
Description
Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE. Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE
Time Frame
Every 4 weeks during treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed myelofibrosis with myeloid metaplasia (MMM), including any of the following subtypes: Agnogenic myeloid metaplasia Post-polycythemic myeloid metaplasia Post-thrombocythemic myeloid metaplasia Evaluable and symptomatic disease, defined as 1 of the following: Anemia (hemoglobin < 10 g/dL or erythrocyte transfusion-dependent, requiring 1 transfusion ≤ 8 weeks) Treatment required* for symptomatic palpable splenomegaly (palpable hepatomegaly is acceptable if previously splenectomized) NOTE: *Subjective but painful enough to mandate intervention Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard cytogenetics (by peripheral blood or marrow) - Previous demonstration of a lack of this translocation (at any point) is sufficient No advanced malignant hepatic tumors PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 50,000/mm³ Creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 2.0 mg/dL OR direct bilirubin ≤ 2.0 mg/dL if total bilirubin elevated (unless attributed to underlying disease) AST and ALT ≤ 2 times upper limit of normal (unless clinically attributed to hepatic extramedullary hematopoiesis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No baseline peripheral or autonomic neuropathy ≥ grade 2 No condition, including the presence of laboratory abnormalities, that would preclude study compliance No hypersensitivity to mannitol or azacitidine Not incarcerated in a municipality (i.e., county, state, or federal prison) PRIOR CONCURRENT THERAPY: At least 14 days since prior chemotherapy, including interferon alfa, anagrelide, or other myelosuppressive agents At least 14 days since prior systemic corticosteroids At least 14 days since prior investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruben A. Mesa, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Azacitidine in Treating Patients With Myelofibrosis

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