Low-Dose Decitabine in Treating Patients With Symptomatic Myelofibrosis

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Dacogen

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring primary myelofibrosis, secondary myelofibrosis, essential thrombocythemia, polycythemia vera

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic

Outcomes

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.

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)

OS was defined as the time from registration to death of any cause.

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.

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.

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.

Full Information

NCT ID

NCT00630994

First Posted

March 6, 2008

Last Updated

November 25, 2015

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00630994

Brief Title

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

2. Study Status

Record Verification Date

November 2012

Overall Recruitment Status

Terminated

Why Stopped

Stopped due to slow accrual

Study Start Date

March 2008 (undefined)

Primary Completion Date

August 2009 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

Keywords

primary myelofibrosis, secondary myelofibrosis, essential thrombocythemia, polycythemia vera

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Dacogen

Primary Outcome Measure Information:

Title

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.

Description

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)

Time Frame

Every 4 weeks during treatment (up to 16 weeks)

Secondary Outcome Measure Information:

Title

Overall Survival(OS)

Description

OS was defined as the time from registration to death of any cause.

Time Frame

up to 3 years

Title

Time to Disease Progression

Description

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.

Time Frame

up to 3 years

Title

Number of Participants With Constitutional Symptoms

Description

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.

Time Frame

Up to 48 weeks

Title

Number of Participants With Severe Adverse Events

Description

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.

Time Frame

Up to 48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

No

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ruben A. Mesa, MD

Organizational Affiliation

Mayo Clinic

Official's Role

Study Chair

Facility Information:

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

About this trial

Eligibility Criteria

Sites / Locations

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial