Clinical trial NCT00630994: Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis
Official title: Phase II Trial of Low Dose Decitabine (Dacogen) in Patients With Primary Myelofibrosis and Post ET/PV Myelofibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Keywords: primary myelofibrosis
secondary myelofibrosis
essential thrombocythemia
polycythemia vera
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-03-07
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Every 4 weeks during treatment (up to 16 weeks)
Secondary outcomes:
measure: Overall Survival(OS)
timeFrame: up to 3 years
measure: Time to Disease Progression
timeFrame: up to 3 years
measure: Number of Participants With Constitutional Symptoms
timeFrame: Up to 48 weeks
measure: Number of Participants With Severe Adverse Events
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Ruben A. Mesa, MD
role: STUDY_CHAIR
References: