Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF

A Multi-national Open-label Phase II Study of the JAK Inhibitor INC424 in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis

The objective of this study was to determine the efficacy of INC424 as assessed by reduction in spleen volume in patients with primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF. The safety and tolerability of INC424 and the effects of INC424 on patient reported outcomes and the duration of response as assessed by reduction in spleen volume was also assessed.

Study Overview

• Status: Completed
• Conditions: Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jinan, China, 250012
    • Novartis Investigative Site
  • Shanghai, China, 200025
    • Novartis Investigative Site
  • Beijing
    • Beijing, Beijing, China, 100730
      • Novartis Investigative Site
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Novartis Investigative Site
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Novartis Investigative Site
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Novartis Investigative Site
    • Suzhou, Jiangsu, China, 215006
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Novartis Investigative Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 466 8560
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa-city, Ishikawa, Japan, 920-8641
      • Novartis Investigative Site
  • Mie
    • Tsu-city, Mie, Japan, 514-8507
      • Novartis Investigative Site
  • Osaka
    • Suita city, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Tokyo
    • Bunkyo ku, Tokyo, Japan, 113 8655
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160 8582
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Novartis Investigative Site
  • Taipei, Taiwan, 10048
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 333
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years or older
2. Diagnosis of primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF
3. Enlarged spleen, measuring 5 cm or greater from the costal margin

4. Must have two or more of the following risk factors:

   1. Over 65 years old
   2. Have the following symptoms often associated with MF: loss of weight, fever, night sweats
   3. Have a low red blood cell count (anemia - hemoglobin < 10 g/dL)
   4. Have a high white blood cell count (history of white blood cell count > 25,000/uL)
   5. Have high circulating blasts (> or = 1%) as measured by blood tests
5. Should have circulating blasts <10% (as measured by blood tests)
6. Should be capable of self-care
7. Should have adequate bone marrow reserve
8. Should not have the option of stem cell transplantation
9. Should discontinue any prior or ongoing treatment for myelofibrosis prior to entering the study
10. Had no prior treatment with another JAK inhibitor

Exclusion Criteria:

1. Does not have adequate liver or kidney function (as measured by blood tests)
2. Has an active infection (bacterial, viral, etc.)
3. Has active hepatitis A, B, or C or positive for HIV
4. Has another cancer that needs active intervention
5. Had a history of bleeding disorder
6. Had a history of very low platelet counts (as measured by blood tests) not related to treatment of MF
7. Had radiation of the spleen within 1 year of joining the study
8. Does not have adequate heart function
9. Sufficient time has elapsed between stopping previous treatment for MF and joining the study
10. Females who are pregnant or breast-feeding
11. Not able to sign informed consent
12. Has any other active medical conditions that the doctor deems may compromise your safety or ability to join in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ruxolitinib; Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.	Drug: Ruxolitinib; INC424 Tablet for oral use, provided in 5 mg bottles. The dosage strength was 5 mg/tablet INC424 phosphate (free base equivalent).; Other Names: INC424

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24	The primary measure of spleen size was by MRI. MRIs were performed with a body coil because the objective was to measure organ volume only, not to assess for lesions. MRIs were performed by local radiologists who were instructed not to provide a quantitative measure of spleen volume, but could provide a qualitative assessment such as enlarged, smaller, larger, etc. The scans from an individual patient were to be read by a central reader upon transfer from the site radiologist.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response	The best response rate was defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline at any post-baseline assessment. The best response rate was estimated with an associated 95% confidence interval.	Weeks 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, at any time point
Kaplan Meier Estimates of Duration of Response of at Least ≥ 35% Reduction From Baseline in Spleen Volume Per Kaplan Meier Estimates	For patients who had at least one ≥ 35% reduction in spleen volume from baseline at postbaseline, the duration of response was calculated. The start date of the duration was defined as the first spleen volume measurement that was ≥ 35% reduction from baseline, and the end date of the response duration was defined as the earliest of the following: death, A ≥ 25% increase in spleen volume by MRI (or CT in applicable patients) compared to baseline, Splenic irradiation, Leukemic transformation as defined by a bone marrow or a peripheral blood blast count of ≥ 20%, Splenectomy. Duration of response is calculated only for participants who achieved at least one measured >= 35% reduction in spleen volume at any time.	Weeks 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240
Change in EORTC QLQ-C30 Scores From Baseline in at Week 24	Patient reported outcomes regarding the impact of MF on patients were assessed using the EORTC QLQ-C30. Data from the EORTC QLQ-C30 questionnaire was analyzed using the standardized scores. There were 2 categories to this scale: Functional/QOL scale and Symptom and Other items scale. For each sub-scale, the raw scores were standardized in order to obtain scores ranging from 0 to 100. For Functional/QOL subscales: a higher score represents a higher/better level of functioning. For Symptoms and Other items subscales: a higher score represents worse level of symptoms. The absolute change from baseline was calculated for each scale and summarized descriptively by scheduled visit.	Baseline, Week 24
Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0	The Seven-day modified MFSAF v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. Symptoms of myelofibrosis (MF) were assessed using this instrument & included filling up quickly/early satiety, abdominal discomfort, pain under the ribs, night sweats, itching, bone/muscle pain & inactivity. The first 6 items assessed MF symptom severity at its worst as recalled & the seventh captured MF-related inactivity in the 7 days prior to the clinic visit assessment. All 7 items asked subjects to record their answers on an 11-point numeric rating scale (NRS) (0=Absent, 10=Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score, defined as the sum of the 6 individual symptom scores other than the inactivity score (each with 0-10 point scale) collected on the same week. The total symptom scale ranges from 0 -60 where higher score indicates a worse level of the condition.	Baseline, Week 24

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Jin J, Du X, Zhou DB, Li JM, Li JY, Hou M, Liu T, Wu DP, Hu Y, Xiao ZJ. [Efficacy and safety of JAK inhibitor ruxolitinib in Chinese patients with myelofibrosis: results of a 1-year follow-up of A2202]. Zhonghua Xue Ye Xue Za Zhi. 2016 Oct 14;37(10):858-863. doi: 10.3760/cma.j.issn.0253-2727.2016.10.007. Chinese.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 14, 2010
• Primary Completion (ACTUAL): October 31, 2017
• Study Completion (ACTUAL): October 31, 2017

Study Registration Dates

• First Submitted: July 11, 2011
• First Submitted That Met QC Criteria: July 11, 2011
• First Posted (ESTIMATE): July 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): September 3, 2019
• Last Update Submitted That Met QC Criteria: August 29, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Ruxolitinib; Myelofibrosis; INC424; MF; post-ET MF; post-PV MF; Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: CINC424A2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No