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
  Purpose

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.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Secondary Myelofibrosis
Drug: Dacogen
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Low Dose Decitabine (Dacogen) in Patients With Primary Myelofibrosis and Post ET/PV Myelofibrosis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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)



Secondary Outcome Measures:
  • 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.


Enrollment: 4
Study Start Date: March 2008
Study Completion Date: April 2012
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00630994

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Ruben A. Mesa, MD Mayo Clinic
  More Information

No publications provided

Responsible Party: Ruben A. Mesa, M.D., Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier: NCT00630994     History of Changes
Other Study ID Numbers: CDR0000588839, P30CA015083, MC0788, NCI-2009-01330, 07-005296
Study First Received: March 6, 2008
Results First Received: January 9, 2012
Last Updated: November 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
primary myelofibrosis
secondary myelofibrosis
essential thrombocythemia
polycythemia vera

Additional relevant MeSH terms:
Myeloproliferative Disorders
Primary Myelofibrosis
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on October 29, 2014