Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01732445
First received: November 19, 2012
Last updated: June 5, 2014
Last verified: June 2014

November 19, 2012
June 5, 2014
April 2013
November 2014   (final data collection date for primary outcome measure)
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.
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 [CR], partial response [PR], or clinical improvement [CI]) 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.
Complete list of historical versions of study NCT01732445 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 [ 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.
  • 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).
Not Provided
 
Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
  • Anemia
  • Primary Myelofibrosis
  • Secondary Myelofibrosis
  • 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
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.
Interventions:
  • Drug: ruxolitinib phosphate
  • Drug: danazol
  • Other: quality-of-life assessment
  • Other: questionnaire administration
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
28
Not Provided
November 2014   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
United States
 
NCT01732445
MC1283, NCI-2012-02201, MC1283, P30CA015083
Yes
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Ruben Mesa Mayo Clinic in Arizona
Mayo Clinic
June 2014

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