Azacitidine in Treating Patients With Myelofibrosis

Chronic Myeloproliferative Disorders Clinical Trial

Official title:

Phase II Study of Azacitidine in Myelofibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00381693
• Other study ID #: CDR0000503972
• Secondary ID: P30CA015083MC058
• Status: Terminated
• Phase: Phase 2
• First received: September 26, 2006
• Last updated: April 19, 2011
• Start date: August 2006
• Est. completion date: April 2009

Study information

• Verified date: April 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: April 2009
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Myeloproliferative Disorders
• Primary Myelofibrosis
• Secondary Myelofibrosis

Intervention

Drug:
• azacitidine

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	4 months	No
Secondary	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.	From date of registration until death or 3 years after registration if patient is still alive	No
Secondary	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.	up to 3 years	No
Secondary	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	Every 4 weeks during treatment	Yes