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

NCT01392443 | Completed Phase 2 Results DMC

• 1 other identifier: CINC424A2202
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 26

Brief Summary

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.

Conditions

Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF

Keywords

Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF; post-PV MF; post-ET MF; INC424; Ruxolitinib; Myelofibrosis; MF

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response

  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

  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

  Baseline, Week 24

• Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0

  Baseline, Week 24

Study Arms (1)

Ruxolitinib

EXPERIMENTAL

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

Interventions

Ruxolitinib DRUG

INC424 Tablet for oral use, provided in 5 mg bottles. The dosage strength was 5 mg/tablet INC424 phosphate (free base equivalent).

Also known as: INC424

Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• years or older
• Diagnosis of primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF
• Enlarged spleen, measuring 5 cm or greater from the costal margin
• Must have two or more of the following risk factors:
• Over 65 years old
• Have the following symptoms often associated with MF: loss of weight, fever, night sweats
• Have a low red blood cell count (anemia - hemoglobin \< 10 g/dL)
• Have a high white blood cell count (history of white blood cell count \> 25,000/uL)
• Have high circulating blasts (\> or = 1%) as measured by blood tests
• Should have circulating blasts \<10% (as measured by blood tests)
• Should be capable of self-care
• Should have adequate bone marrow reserve
• Should not have the option of stem cell transplantation
• Should discontinue any prior or ongoing treatment for myelofibrosis prior to entering the study
• Had no prior treatment with another JAK inhibitor

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (26)

Novartis Investigative Site

Beijing, Beijing Municipality, 100730, China

Location

Novartis Investigative Site

Guangzhou, Guangdong, 51000, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430030, China

Location

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

Location

Novartis Investigative Site

Suzhou, Jiangsu, 215006, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300020, China

Location

Novartis Investigative Site

Hangzhou, Zhejiang, 310003, China

Location

Novartis Investigative Site

Jinan, 250012, China

Location

Novartis Investigative Site

Shanghai, 200025, China

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466 8560, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

Location

Novartis Investigative Site

Maebashi, Gunma, 371 8511, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Novartis Investigative Site

Tsu, Mie-ken, 514-8507, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565 0871, Japan

Location

Novartis Investigative Site

Bunkyo Ku, Tokyo, 113 8655, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160 8582, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Seoul, Seocho Gu, 06591, South Korea

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 03722, South Korea

Location

Novartis Investigative Site

Kaohsiung City, 833, Taiwan

Location

Novartis Investigative Site

Taipei, 10048, Taiwan

Location

Novartis Investigative Site

Taoyuan District, 333, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 27801315 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 11, 2011
• First Posted: July 12, 2011
• Study Start: October 14, 2010
• Primary Completion: October 31, 2017
• Study Completion: October 31, 2017
• Last Updated: September 3, 2019
• Results First Posted: September 3, 2019

Record last verified: 2019-08

Locations

JP (9); TW (3); CN (10); KR (4)