Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01732445
First received: November 19, 2012
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

This phase II pilot trial studies how well ruxolitinib phosphate and danazol work in treating anemia in patients with myelofibrosis. Ruxolitinib phosphate and danazol may cause the body to make more red blood cells. They are used to treat anemia in patients with myelofibrosis.


Condition Intervention Phase
Anemia
Primary Myelofibrosis
Secondary Myelofibrosis
Drug: ruxolitinib phosphate
Drug: danazol
Other: quality-of-life assessment
Other: questionnaire administration
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Phase 2 Pilot Trial of Ruxolitinib Combined With Danazol for Patients With Primary Myelofibrosis (MF), Post Essential Thrombocythemia-Myelofibrosis (Post ET) and Post Polycythemia Vera Myelofibrosis (PV MF) Suffering From Anemia

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Best overall response rate as determined by International Working Group criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The proportion of successes will be estimated by the number of successes (defined as complete response, partial response, or clinical improvement) divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.


Secondary Outcome Measures:
  • Survival time [ Time Frame: From registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  • Adverse event rate(s), assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.


Other Outcome Measures:
  • Change in patient-reported symptoms assessed using the MPN-SAF [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]
    Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range. The MPN-SAF will be analyzed using published scoring algorithms. Graphical procedures will include stream plots of individual patient scores and plots of average values over time. Correlational analyses will be done to determine the relationships among patients-reported symptoms and QOL, as well as with clinical outcomes (best overall response and overall survival) and clinician-assessed symptoms (NCI CTCAE v4).

  • Change in QOL assessed using the EORTC QLQ-C30 [ Time Frame: Baseline to up to 2 years ] [ Designated as safety issue: No ]
    QOL will be described at each time point using the mean, confidence interval, median, and range. The EORTC QLQ-C30 will be analyzed using published scoring algorithms. Graphical procedures will include stream plots of individual patient scores and plots of average values over time. Correlational analyses will be done to determine the relationships among patients-reported symptoms and QOL, as well as with clinical outcomes (best overall response and overall survival) and clinician-assessed symptoms (NCI CTCAE v4).


Estimated Enrollment: 28
Study Start Date: April 2013
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Supportive care (ruxolitinib phosphate and danazol)
Patients receive ruxolitinib phosphate PO BID and danazol PO TID on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.
Drug: ruxolitinib phosphate
Given PO
Other Names:
  • INCB18424
  • Jakafi
  • oral JAK inhibitor INCB18424
  • oral Janus-associated kinase inhibitor INCB18424
Drug: danazol
Given PO
Other Names:
  • Chronogyn
  • DAN
  • Danocrine
Other: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Other: laboratory biomarker analysis
Correlative

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (best overall response) of ruxolitinib (ruxolitinib phosphate) and danazol in patients with myelofibrosis suffering from anemia.

SECONDARY OBJECTIVES:

I. To evaluate the overall survival of patients with myelofibrosis suffering from anemia initiating ruxolitinib and danazol.

II. To evaluate the adverse event profile of ruxolitinib and danazol in patients with myelofibrosis suffering from anemia.

TERTIARY OBJECTIVES:

I. To evaluate quality of life (QOL) and patient-reported symptoms using the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) with ruxolitinib and danazol for patients with myelofibrosis suffering from anemia.

OUTLINE:

Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) and danazol PO thrice daily (TID) on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. At the treating physician's discretion, patients may continue treatment past 6 courses if they are without disease progression.

After completion of study treatment, patients are followed up every 6 months for 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histological confirmation of primary myelofibrosis (MF), post polycythemia vera (PV) or post essential thrombocythemia (ET) myelofibrosis (intermediate 1, intermediate II or high risk) requiring medical therapy
  • Anemia is required for trial entry (defined as hemoglobin < 10g/dL or transfusion dependent [having needed a transfusion anytime in the past 6 months])
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at study entry
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 50,000/uL
  • Serum creatinine =< 1.5 x the upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN; if total bilirubin is > 1.5 x ULN, a direct bilirubin should be performed and must be < 1.5mg/dL
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x ULN; higher values (i.e., =< 5 x ULN) are allowed if clinically compatible with hepatic extramedullary hematopoiesis
  • Life expectancy of >= 6 months
  • Patient able to provide voluntary written informed consent to participate
  • Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only

Exclusion Criteria:

  • Any chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide, interferon-alpha), immunosuppressive therapy, corticosteroids > 10 mg/day prednisone or equivalent, or growth factor treatment (e.g., erythropoietin), hormones (e.g., androgens, danazol) =< 14 days prior to registration; note: patients who are on ruxolitinib may continue on without a 14 day wash out at the treating physician's discretion
  • Major surgery =< 28 days or radiation =< 6 months prior to registration
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Active acute infection requiring antibiotics
  • Uncontrolled congestive heart failure (New York Heart Association classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass, graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to registration
  • Participation in any study of an investigational agent (drug, biologic, device) =< 30 days, unless during non-treatment phase
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness
  • Clinically active hepatitis B or C
  • Active malignancy other than MF, except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ or other malignancies that have been stable and off therapy for 5 years
  • Patient currently taking simvastatin, or lovastatin at a dose greater than 10 mg/day
  • Men with prostate specific antigen (PSA) > 4 ng/ml or with uncontrolled benign prostatic hypertrophy
  • Patient received prior combination treatment with ruxolitinib and danazol together; note: previous treatment with ruxolitinib and/or danazol as single agent therapy is allowed
  • Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); use of the following strong or moderate inhibitors are prohibited =< 7 days prior to registration

    • Strong inhibitors of CYP3A4:

      • Indinavir (Crixivan)
      • Nelfinavir (Viracept)
      • Atazanavir (Reyataz)
      • Clarithromycin (Biaxin, Biaxin XL)
      • Itraconazole (Sporanox)
      • Ketoconazole (Nizoral)
      • Nefazodone (Serzone)
      • Saquinavir (Fortovase, Invirase)
      • Telithromycin (Ketek)
    • Moderate inhibitors of CYP3A4

      • Erythromycin (Erythrocin, E.E.S., Ery-Tab, Eryc, EryPed, PCE)
      • Fluconazole (Diflucan)
      • Grapefruit juice
      • Verapamil (Calan, Calan SR, Covera-HS, Isoptin SR, Verelan)
      • Verelan PM
      • Diltiazem (Cardizem, Cardizem CD, Cardizem LA, Cardizem SR, Cartia XT, Dilacor XR, Diltia XT, Taztia XT, Tiazac)
  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: NCT01732445

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, New York
Tisch Cancer Center
New York, New York, United States, 10029
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Ruben Mesa Mayo Clinic in Arizona
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01732445     History of Changes
Other Study ID Numbers: MC1283, NCI-2012-02201, MC1283, P30CA015083
Study First Received: November 19, 2012
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Primary Myelofibrosis
Anemia
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Danazol
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014