Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis

Chronic Myeloproliferative Disorders Clinical Trial

Official title:

Phase II Trial of Low Dose Decitabine (Dacogen) in Patients With Primary Myelofibrosis and Post ET/PV Myelofibrosis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00630994
• Other study ID #: CDR0000588839
• Secondary ID: P30CA015083MC078
• Status: Terminated
• Phase: Phase 2
• First received: March 6, 2008
• Last updated: November 25, 2015
• Start date: March 2008
• Est. completion date: April 2012

Study information

• Verified date: November 2012
• 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 decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying the side effects and how well low-dose decitabine works in treating patients with symptomatic myelofibrosis.

Description:

OBJECTIVES:

• Determine the efficacy and safety of low-dose decitabine in patients with symptomatic primary myelofibrosis (PMF) or post essential thrombocythemic (ET) or polycythemic vera (PV) myelofibrosis.

• Analyze the ability of this drug to decrease pathologic angiogenesis and other stromal reactive features intrinsic to PMF or post ET/PV myelofibrosis.

OUTLINE: Patients receive low-dose decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving partial remission, complete remission, or clinical improvement may receive up to 12 courses of decitabine in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 3 years.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: April 2012
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histological confirmation of primary myelofibrosis or post essential thrombocythemic or polycythemic vera myelofibrosis

• Reticulin fibrosis = grade 1

• Evaluable and symptomatic disease worthy of treatment, characterized by = 1 of the following:

• Anemia, defined as hemoglobin < 11 g/dL or erythrocyte transfusion dependence

• Palpable and symptomatic splenomegaly (palpable and symptomatic hepatomegaly is acceptable if previously splenectomized)

• Severe, disease-related constitutional symptoms, including = 1 of the following:

• Severe night sweats

• Fevers

• Weight loss

• Bone pain

• Absence of t(9;22) by fluorescent in situ hybridization (FISH) or standard cytogenetics OR prior demonstration of a lack of this translocation

PATIENT CHARACTERISTICS:

• Eastern Co-operative Oncology Group (ECOG) performance status 0-3

• Absolute neutrophil count (ANC) = 1,000/mm³

• Platelet count = 50,000/mm³

• Creatinine = 2.0 mg/dL

• Direct or total bilirubin = 2.0 mg/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 times upper limit of normal (ULN) (= 5 times ULN if elevation is attributed to hepatic extramedullary hematopoiesis)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Not incarcerated in a municipality, county, state, or federal prison

• No serious medical condition or psychiatric illness that would preclude signing the informed consent

• No condition that, in the opinion of the treating physician, places the patient at unacceptable risk for study participation or confounds the ability to interpret study data

• Able to adhere to the study visit schedule and other study requirements

PRIOR CONCURRENT THERAPY:

• No other concurrent chemotherapy (e.g., hydroxyurea, thalidomide, interferon alpha, anagrelide, or other myelosuppressive agent) or experimental therapy

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dacogen

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

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	Number of Participants Who Achieve a Confirmed Response (Complete Remission (CR), Partial Remission (PR), or Clinical Improvement (CI)), According to International Working Group (IWG) Consensus Criteria.	Confirmed response: objective status of CR, PR, or CI on 2 consecutive evaluations >=4 weeks apart.; CR:Complete resolution of disease-related symptoms and signs; peripheral blood count remission; normal leukocyte differential; bone marrow histologic remission.; PR: All criteria for CR except the bone marrow histologic remission. CI: one of the following in the absence of both disease progression and CR/PR: minimum (MI) 20-g/L increase (INC) in hemoglobin level; MI 50% reduction in palpable splenomegaly (>=10cm); MI 100% INC in platelet count(>=50000x10^9/L) or ANC (>=0.5x10^9/L)	Every 4 weeks during treatment (up to 16 weeks)	No
Secondary	Overall Survival(OS)	OS was defined as the time from registration to death of any cause.	up to 3 years	No
Secondary	Time to Disease Progression	Time to disease progression is defined as the time from registration to progression of disease or death due to any cause.; Progression was defined as any one or more of the following: 1)progressive splenomegaly; 2) leukemic transformation confirmed by a bone marrow blast count of >= 20%; 3) an increase in peripheral blood blast percentage of >=20% that lasts for >= 8 weeks.	up to 3 years	No
Secondary	Number of Participants With Constitutional Symptoms	Constitutional symptoms including the presence of one or more of the following felt to be attributed to the disease: severe night sweats, fevers, weight loss and bone pain. Symptoms were assessed every cycle during treatment.	Up to 48 weeks	Yes
Secondary	Number of Participants With Severe Adverse Events	Severe adverse events were defined as grade 3 or higher, regardless of attribution to study drugs. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Adverse events were assessed every cycle during treatment.	Up to 48 weeks	Yes