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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ruxolitinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Myelofibrosis (MF) focused on measuring Primary Myelofibrosis (MF), Post-Polycythemia Vera (PV) MF, Post-Essential Thrombocythemia (ET) MF, post-PV MF, post-ET MF, INC424, Ruxolitinib, Myelofibrosis, MF

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
July 11, 2011
Last Updated
August 29, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01392443
Brief Title
Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
October 14, 2010 (Actual)
Primary Completion Date
October 31, 2017 (Actual)
Study Completion Date
October 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ruxolitinib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
INC424
Intervention Description
INC424 Tablet for oral use, provided in 5 mg bottles. The dosage strength was 5 mg/tablet INC424 phosphate (free base equivalent).
Primary Outcome Measure Information:
Title
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response
Description
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.
Time Frame
Weeks 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, at any time point
Title
Kaplan Meier Estimates of Duration of Response of at Least ≥ 35% Reduction From Baseline in Spleen Volume Per Kaplan Meier Estimates
Description
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.
Time Frame
Weeks 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240
Title
Change in EORTC QLQ-C30 Scores From Baseline in at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0
Description
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.
Time Frame
Baseline, Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 18 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Novartis Investigative Site
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
51000
Country
China
Facility Name
Novartis Investigative Site
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Novartis Investigative Site
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Novartis Investigative Site
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Facility Name
Novartis Investigative Site
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Facility Name
Novartis Investigative Site
City
Jinan
ZIP/Postal Code
250012
Country
China
Facility Name
Novartis Investigative Site
City
Shanghai
ZIP/Postal Code
200025
Country
China
Facility Name
Novartis Investigative Site
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466 8560
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Maebashi city
State/Province
Gunma
ZIP/Postal Code
371 8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Kanazawa-city
State/Province
Ishikawa
ZIP/Postal Code
920-8641
Country
Japan
Facility Name
Novartis Investigative Site
City
Tsu-city
State/Province
Mie
ZIP/Postal Code
514-8507
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita city
State/Province
Osaka
ZIP/Postal Code
565 0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Bunkyo ku
State/Province
Tokyo
ZIP/Postal Code
113 8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160 8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Seocho Gu
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing 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
Citations:
PubMed Identifier
27801315
Citation
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.
Results Reference
derived

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

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