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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04472598




Registration number
NCT04472598
Ethics application status
Date submitted
14/07/2020
Date registered
15/07/2020
Date last updated
27/06/2024

Titles & IDs
Public 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
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study Of Navitoclax In Combination With Ruxolitinib Versus Ruxolitinib In Subjects With Myelofibrosis (TRANSFORM-1)
Secondary ID [1] 0 0
2020-000097-15
Secondary ID [2] 0 0
M16-191
Universal Trial Number (UTN)
Trial acronym
TRANSFORM-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis (MF) 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Navitoclax
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Placebo for Navitoclax

Experimental: Navitoclax + Ruxolitinib - Participants will receive Navitoclax in combination with Ruxolitinib

Active comparator: Placebo for Navitoclax + Ruxolitinib - Participants will receive placebo for Navitoclax and Ruxolitinib


Treatment: Drugs: Navitoclax
Tablet; Oral

Treatment: Drugs: Ruxolitinib
Tablet; Oral

Treatment: Drugs: Placebo for Navitoclax
Tablet; Oral
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24)
Timepoint [1] 0 0
At Week 24
Secondary outcome [1] 0 0
Change in Total Symptom Score (TSS)
Timepoint [1] 0 0
Baseline (Week 0) Up to Week 24
Secondary outcome [2] 0 0
Percentage of Participants who achieve Spleen Volume Reduction of at least 35% (SVR35)
Timepoint [2] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [3] 0 0
Duration of 35% Spleen Volume Reduction (SVR35)
Timepoint [3] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [4] 0 0
Change In Fatigue
Timepoint [4] 0 0
Baseline (Week 0) Up to Week 24
Secondary outcome [5] 0 0
Change in Physical Functioning
Timepoint [5] 0 0
Baseline (Week 0) Up to Week 24
Secondary outcome [6] 0 0
Percentage of Participants who achieve Anemia Response
Timepoint [6] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [7] 0 0
Overall Survival (OS)
Timepoint [7] 0 0
Up To approximately 8 Years
Secondary outcome [8] 0 0
Leukemia-Free Survival
Timepoint [8] 0 0
Up To approximately 8 Years
Secondary outcome [9] 0 0
Percentage of Participants who Achieve Reduction in Grade of Bone Marrow Fibrosis
Timepoint [9] 0 0
Baseline (Week 0) Up to Week 96

Eligibility
Key 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 immediately preceding the date of 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 and other criteria per National Comprehensive Cancer Network guidelines.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with a Janus Kinase-2 (JAK-2) inhibitor.
* Prior treatment with a B-cell lymphoma 2 homology 3 (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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
29/01/2025
Actual
Sample size
Target
Accrual to date
Final
252
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Kinghorn Cancer Centre /ID# 221503 - Darlinghurst
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit Albury Wodonga Regional Cancer Centre /ID# 231311 - East Albury
Recruitment hospital [3] 0 0
Gosford Hospital /ID# 221499 - Gosford
Recruitment hospital [4] 0 0
Liverpool Hospital /ID# 221803 - Liverpool
Recruitment hospital [5] 0 0
Townsville University Hospital /ID# 229794 - Douglas
Recruitment hospital [6] 0 0
Peter MacCallum Cancer Ctr /ID# 229795 - Melbourne
Recruitment hospital [7] 0 0
Alfred Health /ID# 221501 - Melbourne
Recruitment hospital [8] 0 0
Royal Perth Hospital /ID# 223203 - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2640 - East Albury
Recruitment postcode(s) [3] 0 0
2250 - Gosford
Recruitment postcode(s) [4] 0 0
2170 - Liverpool
Recruitment postcode(s) [5] 0 0
4814 - Douglas
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
6000 - Perth
Recruitment outside Australia
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Taoyuan City
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Turkey
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Ankara
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Edirne, Istanbul
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Istanbul
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Izmir
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Lviv
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United Kingdom
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Lincolnshire
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London, City Of
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Oxfordshire
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Birmingham
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/study/NCT04472598
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04472598