Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis

This study has been terminated.
(Stopped due to slow accrual)
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00630994
First received: March 6, 2008
Last updated: November 9, 2012
Last verified: November 2012

March 6, 2008
November 9, 2012
March 2008
August 2009   (final data collection date for primary outcome 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. [ Time Frame: Every 4 weeks during treatment (up to 16 weeks) ] [ Designated as safety issue: No ]

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)

Confirmed response rate (complete remission, partial remission, or clinical improvement) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00630994 on ClinicalTrials.gov Archive Site
  • Overall Survival(OS) [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
    OS was defined as the time from registration to death of any cause.
  • Time to Disease Progression [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

    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.

  • Number of Participants With Constitutional Symptoms [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: Yes ]
    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.
  • Number of Participants With Severe Adverse Events [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: Yes ]
    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.
  • Overall survival [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Constitutional symptoms [ Designated as safety issue: Yes ]
  • Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Pertinent biologic characteristics of primary myelofibrosis as assessed before and during treatment with decitabine [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis
Phase II Trial of Low Dose Decitabine (Dacogen) in Patients With Primary Myelofibrosis and Post ET/PV Myelofibrosis

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Myeloproliferative Disorders
  • Secondary Myelofibrosis
Drug: Dacogen
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
April 2012
August 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00630994
CDR0000588839, P30CA015083, MC0788, NCI-2009-01330, 07-005296
Yes
Ruben A. Mesa, M.D., Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Ruben A. Mesa, MD Mayo Clinic
Mayo Clinic
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP