Ruxolitinib Phosphate and Danazol in Treating Anemia in Patients With Myelofibrosis

NCT01732445 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1283NCI-2012-02201P30CA015083
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Anemia; Primary Myelofibrosis; Secondary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate as Determined by International Working Group Criteria

  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 Outcomes (2)

• Survival Time

  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)

  Up to 2 years

Other Outcomes (1)

• 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

  Baseline to up to 2 years

Study Arms (1)

Supportive care (ruxolitinib phosphate and danazol)

EXPERIMENTAL

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; Drug: danazol; Other: quality-of-life assessment; Other: questionnaire administration

Interventions

ruxolitinib phosphate DRUG

Given PO

Also known as: INCB18424, Jakafi, oral JAK inhibitor INCB18424, oral Janus-associated kinase inhibitor INCB18424

Supportive care (ruxolitinib phosphate and danazol)

danazol DRUG

Given PO

Also known as: Chronogyn, DAN, Danocrine

Supportive care (ruxolitinib phosphate and danazol)

quality-of-life assessment OTHER

Ancillary studies

Also known as: quality of life assessment

Supportive care (ruxolitinib phosphate and danazol)

questionnaire administration OTHER

Ancillary studies

Supportive care (ruxolitinib phosphate and danazol)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Tisch Cancer Center

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Anemia; Primary Myelofibrosis

Interventions

ruxolitinib; Danazol

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Ruben A. Mesa, M.D.
• Organization: Mayo Clinic

mesa.ruben@mayo.edu

480/301-8335

Study Officials

• Ruben Mesa

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: April 1, 2013
• Primary Completion: July 14, 2016
• Study Completion: August 10, 2017
• Last Updated: October 18, 2017
• Results First Posted: October 18, 2017

Record last verified: 2017-05

Locations

US (2)