Azacitidine in Treating Patients With Myelofibrosis

This study has been terminated.
(Due to lack of accrual and trial has demonstrated too little clinical benefit)
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00381693
First received: September 26, 2006
Last updated: April 19, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Drug: azacitidine
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Azacitidine in Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

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 [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    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) [ Time Frame: From date of registration until death or 3 years after registration if patient is still alive ] [ Designated as safety issue: No ]
    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 Frame: up to 3 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 4 weeks during treatment ] [ Designated as safety issue: Yes ]

    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



Enrollment: 10
Study Start Date: August 2006
Study Completion Date: April 2009
Primary Completion Date: March 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00381693

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Ruben A. Mesa, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Ruben A. Mesa, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00381693     History of Changes
Other Study ID Numbers: CDR0000503972, P30CA015083, MC058D, 05-004297
Study First Received: September 26, 2006
Results First Received: November 9, 2010
Last Updated: April 19, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
primary myelofibrosis
polycythemia vera
essential thrombocythemia
secondary myelofibrosis

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 26, 2014