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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 : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:

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 130 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), 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 ...

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 14, 2022
Estimated Study Completion Date : July 26, 2028


Arm Intervention/treatment
Experimental: Navitoclax + Ruxolitinib
Participants will receive Navitoclax in combination with Ruxolitinib
Drug: Navitoclax
Tablet; Oral
Other Name: ABT-263

Drug: Ruxolitinib
Tablet; Oral

Active Comparator: Placebo for Navitoclax + Ruxolitinib
Participants will receive placebo for Navitoclax and Ruxolitinib
Drug: Ruxolitinib
Tablet; Oral

Drug: Placebo for Navitoclax
Tablet; Oral




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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 disease progression, or to the date of death, whichever occurs first.

  4. 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.

  5. 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.

  6. Proportion 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.

  7. Overall Survival (OS) [ Time Frame: Up To approximately 5 Years ]
    OS is defined as the time from start of study to the date of death from any cause.

  8. Leukemia-Free Survival [ Time Frame: Up To approximately 5 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of Primary MyeloFibrosis (MF) or Secondary MF (post polycythemia vera [PPV] - MF or Post Essential Thrombocytopenia [PET] - MF) as defined by World Health Organization (WHO) classification.
  • 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.
  • Receiving medication that interferes with coagulation or platelet function except for low dose aspirin (up to 100 milligram daily) and low molecular weight heparin (LMWH) within 3 days prior to the first dose of study drug or during the study treatment period.

Information from the National Library of Medicine

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


Contacts
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Contact: ABBVIE CALL CENTER 844-663-3742 abbvieclinicaltrials@abbvie.com

Locations
Show Show 135 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT04472598    
Other Study ID Numbers: M16-191
2020-000097-15 ( EudraCT Number )
First Posted: July 15, 2020    Key Record Dates
Last Update Posted: March 30, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Myelofibrosis
Navitoclax
Ruxolitinib
Cancer
ABT-263
TRANSFORM-1
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Navitoclax
Antineoplastic Agents