Simplify 2: Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF

Sponsor

Sierra Oncology, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02101268

Collaborator

(none)

156

Enrollment

Locations

Arms

58.2

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to determine the efficacy of momelotinib (MMB) versus best available therapy (BAT) in anemic or thrombocytopenic adults with primary myelofibrosis (PMF), or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF) who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).

Participants will be randomized to receive either MMB or BAT for 24 weeks during the randomized treatment phase, after which they will be eligible to receive MMB in an extended treatment phase for up to an additional 204 weeks. After discontinuation of study medication, assessments will continue for 12 additional weeks, after which participants will be contacted for survival follow-up approximately every 6 months for up to 5 years from the date of enrollment or until study termination. For those subjects planning to continue treatment with MMB following the end of the study, the End of Treatment, 30-day, 12-Week, and survival follow-up visits are not required.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis (PMF) Post-polycythemia Vera (Post-PV) Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)	Drug: Momelotinib Drug: Best Available Therapy (BAT)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

156 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Randomized Study To Evaluate the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis Who Were Treated With Ruxolitinib

Actual Study Start Date :

Jun 19, 2014

Actual Primary Completion Date :

Jul 28, 2016

Actual Study Completion Date :

Apr 25, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: Momelotinib Participants will receive momelotinib for 24 weeks during the randomized treatment phase, after which they will be eligible to receive momelotinib in an extended treatment phase for up to an additional 204 weeks.	Drug: Momelotinib Momelotinib tablet administered orally once daily Other Names: GS-0387 CYT387
Active Comparator: Arm 2: Best Available Therapy (BAT) Participants in the BAT treatment arm will receive treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may be changed at any time during the study except during the screening period. After completion of the randomized treatment phase, participants will be eligible to receive momelotinib for the duration of the study during the extended treatment phase for up to 204 weeks.	Drug: Best Available Therapy (BAT) Regimens for BAT may include but are not limited to chemotherapy (eg hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulating agent, androgen, interferon, and may include no myelofibrosis treatment.

Arm

Intervention/Treatment

Experimental: Arm 1: Momelotinib

Participants will receive momelotinib for 24 weeks during the randomized treatment phase, after which they will be eligible to receive momelotinib in an extended treatment phase for up to an additional 204 weeks.

Drug: Momelotinib

Momelotinib tablet administered orally once daily

Other Names:

GS-0387

CYT387

Active Comparator: Arm 2: Best Available Therapy (BAT)

Participants in the BAT treatment arm will receive treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may be changed at any time during the study except during the screening period. After completion of the randomized treatment phase, participants will be eligible to receive momelotinib for the duration of the study during the extended treatment phase for up to 204 weeks.

Drug: Best Available Therapy (BAT)

Regimens for BAT may include but are not limited to chemotherapy (eg hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulating agent, androgen, interferon, and may include no myelofibrosis treatment.

Outcome Measures

Primary Outcome Measures

Splenic response rate at Week 24 [Week 24]
Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT.

Secondary Outcome Measures

Response rate in total symptom score at Week 24 [Week 24]
Total symptom score (TSS) is defined as the proportion of participants who achieve a ≥ 50% reduction in TSS from baseline to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) v2.0 diary.
Rate of red blood cell (RBC) transfusion through Week 24 [Baseline to Week 24]
Rate of RBC transfusion is defined as the average number of RBC units per participant per month.
RBC transfusion independence rate at Week 24 [Week 24]
RBC transfusion independence is the proportion of participants who are transfusion independent at Week 24, defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the prior 12 weeks.
RBC transfusion dependence rate at Week 24 [Week 24]
RBC transfusion dependence is the proportion of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the prior 8 weeks.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Palpable splenomegaly at least 5 cm below left costal margin
Confirmed diagnosis of PMF in accordance, or Post-PV/ET MF
Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by
Requirement for RBC transfusion while on ruxolitinib treatment, OR
Dose adjustment of ruxolitinib to < 20 mg twice daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:
≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 thrombocytopenia, OR
≥ CTCAE Grade 3 anemia, OR
≥ CTCAE Grade 3 hematoma (bleed)
High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
If receiving myelofibrosis therapy, must be on a stable dose of the same regimen for at least 2 weeks prior to screen date and through the screening period
If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
Acceptable laboratory assessments obtained within 14 days prior to Randomization
Absolute neutrophil count (ANC) > 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
Peripheral blood blast count < 10%
Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the upper limit of the normal range (ULN) (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
Calculated creatinine clearance of ≥ 45 mL/min
Direct bilirubin ≤ 2.0 x ULN
Life expectancy > 24 weeks
Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years post-menopausal)
Males and females of childbearing potential must agree to use protocol-specified method(s) of contraception
Females who are nursing must agree to discontinue nursing before the first dose of MMB
Able to understand and willing to sign informed consent form (ICF)

Key Exclusion Criteria:

Prior splenectomy
Splenic irradiation within 3 months prior to Randomization
Use of investigational agent within 28 days prior to Randomization
Prior treatment with MMB
Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Randomization
Uncontrolled inter-current illness, per protocol
Known positive status for human immunodeficiency virus (HIV)
Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
Presence of peripheral neuropathy ≥ CTCAE Grade 2
Unwilling or unable to undergo a MRI or CT Scan per study protocol requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	City	State	Country
1	Los Angeles	California	United States
2	Gainesville	Florida	United States
3	Atlanta	Georgia	United States
4	Kansas City	Kansas	United States
5	Baltimore	Maryland	United States
6	Saint Louis	Missouri	United States
7	Albuquerque	New Mexico	United States
8	New York	New York	United States
9	Durham	North Carolina	United States
10	Winston-Salem	North Carolina	United States
11	Cleveland	Ohio	United States
12	Pittsburgh	Pennsylvania	United States
13	Houston	Texas	United States
14	Edmonton	Alberta	Canada
15	Montreal		Canada
16	Toronto		Canada
17	Lille cedex		France
18	Marseille		France
19	Nantes		France
20	Paris		France
21	Pierre Benite Cedex		France
22	Toulouse		France
23	Villejuif Cedex		France
24	Dresden		Germany
25	Hamburg		Germany
26	Koln		Germany
27	Mannheim		Germany
28	Ashkelon		Israel
29	Haifa		Israel
30	Jerusalem		Israel
31	Tel-Aviv		Israel
32	Bologna		Italy
33	Firenze		Italy
34	Genova		Italy
35	Milano		Italy
36	Novara		Italy
37	Roma		Italy
38	Varese		Italy
39	Badalona		Spain
40	Barcelona		Spain
41	Madrid		Spain
42	Salamanca		Spain
43	Valencia		Spain
44	Zaragoza		Spain
45	Birmingham	England	United Kingdom
46	Leeds	England	United Kingdom
47	Leicester	England	United Kingdom
48	London	England	United Kingdom