Description:
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 till
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.
Title
- Brief Title: 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
- 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)
Clinical Trial IDs
- ORG STUDY ID:
M16-191
- SECONDARY ID:
2020-000097-15
- NCT ID:
NCT04472598
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Navitoclax | ABT-263 | Navitoclax + Ruxolitinib |
Ruxolitinib | | Navitoclax + Ruxolitinib |
Placebo for Navitoclax | | Placebo for Navitoclax + Ruxolitinib |
Purpose
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 till
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Navitoclax + Ruxolitinib | Experimental | Participants will receive Navitoclax in combination with Ruxolitinib | |
Placebo for Navitoclax + Ruxolitinib | Active Comparator | Participants will receive placebo for Navitoclax and Ruxolitinib | - Ruxolitinib
- Placebo for Navitoclax
|
Eligibility Criteria
Inclusion Criteria:
- Documented diagnosis of Primary MyeloFibrosis (MF) as defined by World Health
Organization (WHO) classification or Secondary MF (post polycythemia vera [PPV] - MF
or Post Essential Thrombocytopenia [PET] - MF) .
- Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out
of 7 days prior to randomization.
-- Must have at least 2 symptoms with a score >=3 or a total score of >=12, as
measured by the MFSAF v4.0.
- Classified as intermediate-2, or high-Risk MF as defined by the Dynamic International
Prognostic Scoring System Plus (DIPSS+).
- Has splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below
costal margin or spleen volume greater than or equal to 450 cubic cm as assessed
centrally by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
- Ineligible for stem cell transplantation at time of study entry due to age,
comorbidities, or unfit for unrelated or unmatched donor transplant.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Exclusion Criteria:
- Prior treatment with a Janus Kinase-2 (JAK-2) inhibitor.
- Prior treatment with a BH3-mimetic compound or bromodomain and extra-terminal motif
(BET) inhibitor or stem cell transplant.
- Receiving medication that interferes with coagulation or platelet function within 3
days prior to the first dose of study drug or during the study treatment period except
for low dose aspirin (up to 100 milligram daily) and low molecular weight heparin
(LMWH).
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24) |
Time Frame: | At Week 24 |
Safety Issue: | |
Description: | Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria. |
Secondary Outcome Measures
Measure: | Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) |
Time Frame: | Baseline (Week 0) Up to Week 24 |
Safety Issue: | |
Description: | Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0. |
Measure: | Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35) |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | Reduction in spleen volume is measured by MRI or CT, per IWG criteria. |
Measure: | Duration of 35% Spleen Volume Reduction (SVR35) |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | 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). |
Measure: | Change In Fatigue |
Time Frame: | Baseline (Week 0) Up to Week 24 |
Safety Issue: | |
Description: | Change in fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 7a. |
Measure: | Time to Deterioration of Physical Functioning |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | 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. |
Measure: | Proportion of Participants who achieve Anemia Response |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria. |
Measure: | Overall Survival (OS) |
Time Frame: | Up To approximately 8 Years |
Safety Issue: | |
Description: | OS is defined as the time from the date of randomization to the date of death from any cause. |
Measure: | Leukemia-Free Survival |
Time Frame: | Up To approximately 8 Years |
Safety Issue: | |
Description: | 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. |
Measure: | Overall Response of Clinical Improvement |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | Clinical improvement is defined as the achievement of anemia, spleen, or symptoms response without progressive disease, per International Working Group (IWG) criteria. |
Measure: | Percentage of Participants who achieve reduction in Grade of Bone Marrow Fibrosis |
Time Frame: | Baseline (Week 0) Up to Week 96 |
Safety Issue: | |
Description: | Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | AbbVie |
Trial Keywords
- Myelofibrosis
- Navitoclax
- Ruxolitinib
- Cancer
- ABT-263
- TRANSFORM-1
Last Updated
August 26, 2021