Trial Outcomes & Findings for Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis (NCT NCT01732445)

Last Updated: 2017-10-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2017-10-18

Participant Flow

Participant milestones

Participant milestones
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 Participants Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Age, Continuous	70.5 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Outcome measures

Outcome measures
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 Participants Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Best Overall Response Rate as Determined by International Working Group Criteria	28.6 percentage of patients with CR, PR or CI Interval 8.4 to 58.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 Participants Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Survival Time	19.2 months Interval 4.1 to 28.8

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 Participants Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Platelet count decreased	7.1 percentage of patients
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Anemia	64.3 percentage of patients
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) White blood cell decreased	7.1 percentage of patients
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Neutrophil count decreased	14.3 percentage of patients
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Hypertension	7.1 percentage of patients
Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) Premature menopause	7.1 percentage of patients

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 Participants Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
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	28.6 percentage of patients Interval 8.4 to 58.1

Adverse Events

Supportive Care (Ruxolitinib Phosphate and Danazol)

Serious events: 7 serious events

Other events: 14 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 participants at risk Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Blood and lymphatic system disorders Anemia	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Cardiac disorders Myocardial infarction	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
General disorders General disorders and administration site conditions - Other, specify	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
General disorders Sudden death NOS	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Lung infection	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Investigations Platelet count decreased	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Hyperkalemia	14.3% 2/14 • Number of events 2 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Hyponatremia	14.3% 2/14 • Number of events 2 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Nervous system disorders Intracranial hemorrhage	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Nervous system disorders Transient ischemic attacks	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).

Other adverse events

Other adverse events
Measure	Supportive Care (Ruxolitinib Phosphate and Danazol) n=14 participants at risk Patients receive ruxolitinib phosphate PO 10 mg BID and danazol PO 200 mg 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.
Blood and lymphatic system disorders Anemia	64.3% 9/14 • Number of events 24 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Diarrhea	21.4% 3/14 • Number of events 6 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Gastrointestinal disorders Nausea	21.4% 3/14 • Number of events 6 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
General disorders Edema limbs	14.3% 2/14 • Number of events 2 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Upper respiratory infection	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Infections and infestations Urinary tract infection	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Investigations Alanine aminotransferase increased	14.3% 2/14 • Number of events 2 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Investigations Neutrophil count decreased	28.6% 4/14 • Number of events 5 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Investigations Platelet count decreased	85.7% 12/14 • Number of events 29 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Investigations White blood cell decreased	35.7% 5/14 • Number of events 9 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Anorexia	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Metabolism and nutrition disorders Hyperkalemia	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 2/14 • Number of events 2 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Reproductive system and breast disorders Irregular menstruation	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Reproductive system and breast disorders Premature menopause	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Periorbital edema	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Skin and subcutaneous tissue disorders Photosensitivity	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).
Vascular disorders Hypertension	7.1% 1/14 • Number of events 1 • Up to 2 years CTCAE term (AE description) and grade: The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation and scientific analysis and is a single MedDRA Lowest Level Term (LLT).

Additional Information

Ruben A. Mesa, M.D.

Mayo Clinic

Phone: 480/301-8335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place