Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04468984|
Recruitment Status : Recruiting
First Posted : July 13, 2020
Last Update Posted : April 1, 2021
Myelofibrosis (MF) is a bone marrow illness that affects blood-forming tissues in the body. MF disturbs the body's normal production of blood cells, causing extensive scarring in the bone marrow. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, as 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. The study has 2 arms - A and B. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. Adult participants with a diagnosis of relapsed/refractory (R/R) MF will be enrolled. Approximately 330 participants will be enrolled in approximately 190 sites across the world.
In Arm A, participants will receive oral navitoclax tablet once daily with oral ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT as identified by the investigator. Treatment will continue until clinical benefit is not seen, 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.
|Condition or disease||Intervention/treatment||Phase|
|Myelofibrosis (MF)||Drug: Navitoclax Drug: Ruxolitinib Drug: Best Available Therapy (BAT)||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 :||330 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Navitoclax in Combination With Ruxolitinib Versus Best Available Therapy in Subjects With Relapsed/Refractory Myelofibrosis (TRANSFORM-2)|
|Actual Study Start Date :||August 31, 2020|
|Estimated Primary Completion Date :||February 28, 2022|
|Estimated Study Completion Date :||August 16, 2028|
Experimental: Arm A: Navitoclax + Ruxolitinib
Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.
Other Name: ABT-263
Active Comparator: Arm B: Best Available Therapy (BAT)
Participants will receive one of the BAT options, per the investigator's discretion.
Drug: Best Available Therapy (BAT)
Tablet/Capsule; Oral or Solution for Subcutaneous Injection
- 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 Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
- Duration of 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 disease progression, or to the date of death, whichever occurs first.
- 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 Short Form (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.
- Proportion of Participants who achieved 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 [ Time Frame: Up to approximately 3 years ]Overall survival is defined as the time from start of study to the date of death from any cause.
- Leukemia-Free Survival [ Time Frame: Up to approximately 3 years ]Leukemia free survival is the time from start of study to the date of development of leukemia.
- 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): NCT04468984
|Contact: ABBVIE CALL CENTERemail@example.com|
|Study Director:||AbbVie Inc.||AbbVie|