- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01732445
Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis
A 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
Study Overview
Status
Conditions
Intervention / Treatment
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 2 years.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Arizona
-
Scottsdale, Arizona, United States, 85259
- Mayo Clinic in Arizona
-
-
New York
-
New York, New York, United States, 10029
- Tisch Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Ancillary studies
Ancillary studies
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Overall Response Rate as Determined by International Working Group Criteria
Time Frame: Up to 2 years
|
Best overall response rate as determined by International Working Group criteria: An evaluable patient will be classified as a responder for the primary endpoint if the patient's best overall response is CR, PR or CI (Clinical Improvement) as determined by International Working Group Criteria over all cycles of study treatment.
The percentage 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 times 100.
Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Survival Time
Time Frame: From registration to death due to any cause, assessed up to 2 years
|
Survival time is defined as the time from registration to death due to any cause.
The distribution of survival time will be estimated using the method of Kaplan-Meier.
The median and 95% confidence interval are reported below.
|
From registration to death due to any cause, assessed up to 2 years
|
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Time Frame: Up to 2 years
|
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups.
In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.
The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
|
Up to 2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Patient-reported Symptoms Assessed Using the MPN-SAF, as Measured by the Percentage of Patients With a Decrease in MPN-SAF TSS Greater Than 50% From Baseline
Time Frame: Baseline to up to 2 years
|
Patient-reported symptoms will be described at each time point using the mean, confidence interval, median, and range.
The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) will be analyzed using published scoring algorithms.
MPN-SAF includes 27 items scored on a scale of 0 to 10.
The MPN-SAF Total Symptom Score (TSS) (range 0-100) was computed according to the published scoring algorithm.
Higher scores represent worse symptom burden.
The percentage of patients with a decrease in MPN-SAF TSS greater than 50% from baseline and 95% confidence interval are reported below.
|
Baseline to up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ruben Mesa, Mayo Clinic
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Primary Myelofibrosis
- Anemia
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protein Kinase Inhibitors
- Hormone Antagonists
- Estrogen Antagonists
- Danazol
- Janus Kinase Inhibitors
Other Study ID Numbers
- MC1283 (Other Identifier: Mayo Clinic in Arizona)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2012-02201 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Myelofibrosis
-
Assaf-Harofeh Medical CenterUnknownMyelofibrosis, Primary | Myelofibrosis, Post PV | Myelofibrosis, Post ETIsrael
-
The University of Hong KongRecruitingMyelofibrosis | Primary Myelofibrosis, Prefibrotic StageHong Kong
-
Centre Hospitalier Annecy GenevoisCompleted
-
AbbVieRecruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Puerto Rico, Russian Federation, Serbia, Spain, Taiwan, Turkey, United... and more
-
AbbVieActive, not recruitingMyelofibrosis (MF)United States, Australia, Austria, Belgium, Bulgaria, Canada, Croatia, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Russian Federation, Serbia, South Africa, Spain, Sweden, Taiwan, Turkey and more
-
AbbVieActive, not recruitingMyelofibrosis (MF)United States, Argentina, Australia, Brazil, Bulgaria, Chile, Hungary, Israel, Italy, Japan, Korea, Republic of, Spain, Sweden, Turkey
-
AbbVieTerminatedMyelofibrosis (MF)United States, Korea, Republic of, South Africa
-
National Taiwan University HospitalRecruitingPre-fibrotic MyelofibrosisTaiwan
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.RecruitingModerate and High Risk MyelofibrosisChina
-
Telios Pharma, Inc.RecruitingPrimary Myelofibrosis | Myelofibrosis | Post-PV MF | Post-ET MyelofibrosisSpain, United States, France, Poland, Italy, Germany
Clinical Trials on questionnaire administration
-
Fondazione Don Carlo Gnocchi OnlusUnknown
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)TerminatedHealth Status UnknownUnited States
-
Istanbul Aydın UniversityCompleted
-
Centre Oscar LambretCentre Hospitalier Universitaire de BesanconTerminated
-
Hospital Clínico Universitario de ValladolidRed Centinela Sanitaria de Castilla y León (RCSCYL); Centro Nacional de Gripe... and other collaboratorsRecruitingMigraine | Headache Disorders | Viral Infection | Influenza -Like Illness | Head PainSpain
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingBreast Ductal Carcinoma In Situ | Invasive Breast Carcinoma | COVID-19 Infection | Hereditary Breast CarcinomaUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Recurrent Lymphoma | Recurrent Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Recurrent Plasma Cell Myeloma | Caregiver | Recurrent LeukemiaUnited States
-
I.M. Sechenov First Moscow State Medical UniversityAgency of Social Information St. PetersburgActive, not recruiting
-
I.M. Sechenov First Moscow State Medical UniversityActive, not recruitingShoulder ArthropathyRussian Federation
-
Karolinska University HospitalSahlgrenska University Hospital, Sweden; University Hospital, Linkoeping; Skane...Active, not recruitingQuality of Life | Vulvar CancerSweden