Clinical trial NCT01445769: Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis
Official title: An Open-label Assessment of an Alternative Dosing Strategy of Ruxolitinib in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, and Post-essential Thrombocythemia Myelofibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Keywords: Myelofibrosis
Primary Myelofibrosis
PMF
Post-Polycythemia Vera Myelofibrosis
PPV-MF
Post-Essential Thrombocythemia Myelofibrosis
PET-MF
Open label
Ruxolitinib
18424
Jak inhibitor
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Percentage Change From Baseline in Spleen Volume at Week 24
timeFrame: Baseline to Week 24
measure: Median Percent Change From Baseline in Spleen Volume at Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Mean Percentage Change From Baseline in the Total Symptom Score at Week 24
timeFrame: Baseline to Week 24
measure: Median Percent Change From Baseline in the Total Symptom Score at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With a ≥ 35% Reduction From Baseline in Spleen Volume at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With a ≥ 10% Reduction From Baseline in Spleen Volume at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With a ≥ 50% Improvement From Baseline in Total Symptom Score at Week 24
timeFrame: Baseline to Week 24
measure: Mean Percentage Change From Baseline in Palpable Spleen Length at Week 24
timeFrame: Baseline to Week 24
measure: Median Percent Change From Baseline in Palpable Spleen Length at Week 24
timeFrame: Baseline to Week 24
measure: Percentage of Participants With a ≥ 50% Improvement From Baseline in Their Transfusion Status or With New Transfusion Independence Status for Those Participants Who Were Transfusion Dependent at Baseline
timeFrame: Baseline to Week 24
measure: Percentage of Participants With Clinically Notable Anemia
timeFrame: Baseline to Weeks 12, 18 and 24
measure: Mean Percentage Change in Abdominal Symptom Scores at Week 24.
timeFrame: Week 24
measure: Median Percentage Change in Abdominal Symptom Scores at Week 24.
timeFrame: Week 24
measure: Number of Participants With Grade 3 or Grade 4 Adverse Events
timeFrame: Baseline to the end of the study
Other outcomes:
measure: Dose Distribution at Week 24
timeFrame: Week 24
Locations:
city: Highland
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Orange City
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Morristown
country: United States
state: New Jersey
city: Armonk
country: United States
state: New York
city: Hickory
country: United States
state: North Carolina
city: Canton
country: United States
state: Ohio
city: Hazleton
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Incyte Corporation
name: William V Williams, MD
role: STUDY_DIRECTOR
References:
citation: 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.