Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis (TRANSFORM-1)
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|ClinicalTrials.gov Identifier: NCT04472598|
Recruitment Status : Recruiting
First Posted : July 15, 2020
Last Update Posted : July 29, 2022
Myelofibrosis is a type of bone marrow cancer that usually develops slowly and disrupts body's normal production of blood cells. It causes bone marrow scarring, leading to severe anemia that can cause weakness and fatigue. It can also cause a low number of blood-clotting cells called platelets, which increases risk of bleeding. Myelofibrosis often causes an enlarged spleen. The purpose of this study is to see if a combination of navitoclax and ruxolitinib is more effective and safe in assessment of change in spleen volume when compared to ruxolitinib in participants with myelofibrosis.
Navitoclax is an investigational drug for the treatment of myelofibrosis. Participants in this study are divided into two groups, called treatment arms. Each group receives a different treatment. Adult participants with a diagnosis of myelofibrosis will be enrolled. Around 230 participants will be enrolled in approximately 190 sites worldwide.
Participants will receive oral navitoclax tablet with oral ruxolitinib tablet or oral ruxolitinib tablet with oral placebo (no active drug) tablet and treatment may continue untill the participant cannot tolerate the study drug, or benefit is not achieved, or other reasons which qualify for discontinuation of the study drug.
There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, magnetic resonance imaging (MRI) or computed tomography (CT) scan, bone marrow tests, checking for side effects, and completing questionnaires.
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis (MF)||Drug: Navitoclax Drug: Ruxolitinib Drug: Placebo for Navitoclax||Phase 3|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||230 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Navitoclax In Combination With Ruxolitinib Versus Ruxolitinib In Subjects With Myelofibrosis (TRANSFORM-1)|
|Actual Study Start Date :||September 29, 2020|
|Estimated Primary Completion Date :||January 23, 2023|
|Estimated Study Completion Date :||July 21, 2032|
Experimental: Navitoclax + Ruxolitinib
Participants will receive Navitoclax in combination with Ruxolitinib
Other Name: ABT-263
Active Comparator: Placebo for Navitoclax + Ruxolitinib
Participants will receive placebo for Navitoclax and Ruxolitinib
Drug: Placebo for Navitoclax
- Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24) [ Time Frame: At Week 24 ]Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.
- Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) [ Time Frame: Baseline (Week 0) Up to Week 24 ]Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
- Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35) [ Time Frame: Baseline (Week 0) Up to Week 96 ]Reduction in spleen volume is measured by MRI or CT, per IWG criteria.
- Duration of 35% Spleen Volume Reduction (SVR35) [ Time Frame: Baseline (Week 0) Up to Week 96 ]Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of the first assessment where the spleen volume is less than 35% reduction from baseline and is at least 25% increase from the nadir (the lowest spleen volume).
- Change In Fatigue [ Time Frame: Baseline (Week 0) Up to Week 24 ]Change in fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 7a.
- Time to Deterioration of Physical Functioning [ Time Frame: Baseline (Week 0) Up to Week 96 ]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.
- Percentage of Participants who achieve Anemia Response [ Time Frame: Baseline (Week 0) Up to Week 96 ]The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
- Overall Survival (OS) [ Time Frame: Up To approximately 8 Years ]OS is defined as the time from the date of randomization to the date of death from any cause.
- Leukemia-Free Survival [ Time Frame: Up To approximately 8 Years ]Leukemia-free survival is defined as the number of days from the date of randomization to the onset date of documented leukemia, disease progression due to leukemia, or death due to leukemia, whichever occurs first.
- Overall Response of Clinical Improvement [ Time Frame: Baseline (Week 0) Up to Week 96 ]Clinical improvement is defined as the achievement of anemia, spleen, or symptoms response without progressive disease, per International Working Group (IWG) criteria.
- Percentage of Participants who achieve reduction in Grade of Bone Marrow Fibrosis [ Time Frame: Baseline (Week 0) Up to Week 96 ]Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04472598
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|Study Director:||ABBVIE INC.||AbbVie|