Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, compared to best available therapy, for adult participants with MF. Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. Participants in this study will be randomly selected (like picking numbers out of a hat) to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to pick which treatment arm a participants enters. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. In Arm C, participants will receive navitoclax. Adult participants with a diagnosis of MF that came back or did not get better after earlier treatment will be enrolled. Approximately 330 participants will be enrolled in approximately 322 sites across the world. In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the investigator. In Arm C, participants will receive navitoclax tablet by mouth once daily. Participants will receive the study drug until they experience no benefit (determined by the investigator), participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of treatment will be checked by medical assessments, blood and bone marrow tests, checking for side effects, and completing questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
330
Tablet; Oral
Tablet; Oral
Tablet/Capsule; Oral or Solution for Subcutaneous Injection
Ironwood Cancer & Res Ctr /ID# 222162
Chandler, Arizona, United States
Highlands Oncology Group, PA /ID# 221826
Springdale, Arkansas, United States
City of Hope /ID# 218996
Duarte, California, United States
Providence - St. Jude Medical Center /ID# 271382
Fullerton, California, United States
Moores Cancer Center /ID# 271596
La Jolla, California, United States
Arms A and B: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24)
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Time frame: At Week 24
Arms A and B: Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS)
Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Time frame: Baseline (Week 0) Up to Week 24
Arms A and B: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at any time
Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Time frame: Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Reduction in Grade of Bone Marrow Fibrosis
Reduction in grade of bone marrow fibrosis from baseline as measured by the European consensus grading system will be assessed.
Time frame: Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Anemia Response
Anemia response per International Working Group (IWG) criteria will be assessed.
Time frame: Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with Overall Survival
Overall survival is defined as the time from start of study to the date of death from any cause.
Time frame: Last Visit Up to 5 Years
Arms A and B: Percentage of Participants with Leukemia-free Survival
Leukemia free survival is the time from start of study to the date of development of leukemia.
Time frame: Last Visit Up to 5 Years
Arms A and B: Percentage of Participants with Change in Fatigue
Change in fatigue will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a.
Time frame: Baseline (Week 0) Up to Week 24
Arms A and B: Time to Deterioration of Physical Functioning
Time to deterioration of physical functioning is measured by the physical functioning domain of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, or death.
Time frame: Baseline (Week 0) Up to Week 97
Arms A and B: Percentage of Participants with at Least 50% Reduction in TSS
At least 50% reduction in TSS from baseline (at any time) as measured by MFSAF v4.0.
Time frame: Baseline (Week 0) Up to Week 97
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Moores Cancer Center at UC San Diego /ID# 219009
La Jolla, California, United States
Long Beach Memorial Medical Ct /ID# 224542
Long Beach, California, United States
Icri /Id# 221967
Whittier, California, United States
St. Mary's Hospital Regional Cancer Center /ID# 224229
Grand Junction, Colorado, United States
Augusta University Georgia Cancer Center /ID# 219051
Augusta, Georgia, United States
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