Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis

NCT ID: NCT01445769

Last Updated: 2019-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2013-04-30

Brief Summary

The purpose of this study was to evaluate the effect of an alternative dosing strategy of ruxolitinib in subjects with primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) and post essential thrombocythemia-myelofibrosis (PET-MF) in order to minimize the development of anemia and thrombocytopenia.

Detailed Description

This pilot study was designed to explore an alternative dosing approach with the purpose of reducing anemia and thrombocytopenia. Subjects began dosing at 10 mg bid and had the opportunity for dose increases based on assessments of efficacy and overall hematologic status in a defined prior dosing interval. Dose increases were restricted to those patients who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported Patient's Global Impression of Change (PGIC) score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin had been reduced by less than 40% at that visit relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at Week 12 and to a maximum of 20 mg BID at Week 18. There were also protocol-required dose decreases for thrombocytopenia (platelets <100 x 10^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level < 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).This approach assumed that beginning at a low dose for initial therapy might have a positive impact on the rate of the initial hemoglobin decline and the nadir by decreasing the level of JAK-mediated inhibition of hematopoiesis. Specific dose modifications were described to minimize excursions of hemoglobin levels into the Grade 3 or Grade 4 range.

Conditions

Primary Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ruxolitinib

Participants initially received ruxolitinib 10 mg twice a day (bid) for 24 weeks. Dose increases of 5 mg bid were possible at Weeks 12 and 18 up to a maximum dose of 20 mg bid.

Group Type: EXPERIMENTAL

Ruxolitinib

Intervention Type: DRUG

Ruxolitinib was provided as 5 mg tablets. Dose increases were only permitted at wks 12 \& 18 for lack of efficacy. Increases were restricted to patients who didn't meet criteria for a dose hold over the prior 6 wks, had a platelet count ≥ 100 x 10\^9/L at wk 12 or ≥ 150 x 10\^9/L at wk 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin was reduced by less than 40% relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at wk 12 and to a maximum of 20 mg BID at wk 18. The protocol required dose decreases for thrombocytopenia (platelets \<100 x 10\^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level \< 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).

Interventions

Ruxolitinib

Ruxolitinib was provided as 5 mg tablets. Dose increases were only permitted at wks 12 \& 18 for lack of efficacy. Increases were restricted to patients who didn't meet criteria for a dose hold over the prior 6 wks, had a platelet count ≥ 100 x 10\^9/L at wk 12 or ≥ 150 x 10\^9/L at wk 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length below the costal margin was reduced by less than 40% relative to Baseline. Dose increases were elective and not required. Subjects were permitted a dose increase of 5 mg BID to 15 mg BID at wk 12 and to a maximum of 20 mg BID at wk 18. The protocol required dose decreases for thrombocytopenia (platelets \<100 x 10\^9/L) or protocol-defined anemia (decline in hemoglobin of at least 2 g/dL to a level \< 8 g/dL, development of transfusion dependence, or a 50% increase in transfusion requirements for transfusion dependent subjects).

Intervention Type: DRUG

Other Intervention Names

INCB018424; INC424

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (PPV-MF), or Post-Essential Thrombocythemia Myelofibrosis (PET-MF) as confirmed by bone marrow biopsy.
• Must score at least 2 points on the Dynamic International Prognostic Scoring System (DIPSS) scale for prognostic risk factors.
• Peripheral blast count < 5% at both Screening and Baseline hematology assessments.
• Must discontinue all drugs used to treat underlying myelofibrosis (MF) disease no later than Day -1 (the day prior to starting ruxolitinib).
• Must have hemoglobin value ≥ 6.5 g/dL and be willing to receive blood transfusions.
• Platelet count ≥ 100*10^9/L.
• Must have a palpable spleen.

Exclusion Criteria

• Inadequate liver or bone marrow reserves, end stage renal disease on dialysis, clinically significant concurrent infections requiring therapy, or unstable cardiac function.
• Invasive malignancies over the previous 5 years (except treated early stage carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, and completely resected papillary thyroid and follicular thyroid cancers).
• Splenic irradiation within 6 months prior to receiving the first dose of study medication.
• Life expectancy less than 6 months.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William V Williams, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

Highland, California, United States

La Jolla, California, United States

Los Angeles, California, United States

Jacksonville, Florida, United States

Orange City, Florida, United States

Winter Park, Florida, United States

Atlanta, Georgia, United States

Augusta, Georgia, United States

Iowa City, Iowa, United States

Baltimore, Maryland, United States

Ann Arbor, Michigan, United States

Southfield, Michigan, United States

Morristown, New Jersey, United States

Armonk, New York, United States

Hickory, North Carolina, United States

Canton, Ohio, United States

Hazleton, Pennsylvania, United States

Hershey, Pennsylvania, United States

Charleston, South Carolina, United States

Sioux Falls, South Dakota, United States

San Antonio, Texas, United States

Countries

United States

References

Talpaz M, Erickson-Viitanen S, Hou K, Hamburg S, Baer MR. Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. J Hematol Oncol. 2018 Aug 7;11(1):101. doi: 10.1186/s13045-018-0642-0.

Reference Type: DERIVED

PMID: 30086777 (View on PubMed)

Other Identifiers

18424-261

Identifier Type: -

Identifier Source: org_study_id