Clinical trial NCT00381693: Azacitidine in Treating Patients With Myelofibrosis
Official title: Phase II Study of Azacitidine in Myelofibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Keywords: primary myelofibrosis
polycythemia vera
essential thrombocythemia
secondary myelofibrosis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-09-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 4 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of registration until death or 3 years after registration if patient is still alive
measure: Time to Progression
timeFrame: up to 3 years
measure: Number of Participants With Treatment Related Adverse Events
timeFrame: Every 4 weeks during treatment
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ruben A. Mesa, MD
role: STUDY_CHAIR
References: