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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04472598
Ethics application status
Date submitted
14/07/2020
Date registered
15/07/2020
Date last updated
10/05/2021

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) - Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Timepoint [1] 0 0
At Week 24
Secondary outcome [1] 0 0
Percentage of Participants who achieve at least 50% Reduction in Total Symptom Score (TSS) - Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
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) - Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT), per International Working Group (IWG) criteria.
Timepoint [2] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [3] 0 0
Duration of 35% Spleen Volume Reduction (SVR35) - 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.
Timepoint [3] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [4] 0 0
Change In Fatigue - Change in fatigue will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue SF 7a.
Timepoint [4] 0 0
Baseline (Week 0) Up to Week 24
Secondary outcome [5] 0 0
Time to Deterioration of Physical Functioning - 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.
Timepoint [5] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [6] 0 0
Proportion of Participants who achieve Anemia Response - The rate of anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
Timepoint [6] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [7] 0 0
Overall Survival (OS) - OS is defined as the time from start of study to the date of death from any cause.
Timepoint [7] 0 0
Up To approximately 5 Years
Secondary outcome [8] 0 0
Leukemia-Free Survival - 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.
Timepoint [8] 0 0
Up To approximately 5 Years
Secondary outcome [9] 0 0
Overall Response of Clinical Improvement - Clinical improvement is defined as the achievement of anemia, spleen, or symptoms response without progressive disease, per International Working Group (IWG) criteria.
Timepoint [9] 0 0
Baseline (Week 0) Up to Week 96
Secondary outcome [10] 0 0
Percentage of Participants who achieve reduction in Grade of Bone Marrow Fibrosis - Change in grade of bone marrow fibrosis will be measured per the European consensus grading system through bone marrow biopsy.
Timepoint [10] 0 0
Baseline (Week 0) Up to Week 96

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
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 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.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
St. Vincent's Hospital, Darlinghurst /ID# 221503 - Darlinghurst
Recruitment hospital [2] 0 0
Border Medical Oncology /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
The Townsville Hospital /ID# 229794 - Douglas
Recruitment hospital [6] 0 0
Barwon Health University Hospital Geelong /ID# 221804 - Geelong
Recruitment hospital [7] 0 0
Peter MacCallum Cancer Ctr /ID# 229795 - Melbourne
Recruitment hospital [8] 0 0
The Alfred Hospital /ID# 221501 - Prahran
Recruitment hospital [9] 0 0
Royal Perth Hospital /ID# 223203 - Shenton Park
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
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4814 - Douglas
Recruitment postcode(s) [6] 0 0
3220 - Geelong
Recruitment postcode(s) [7] 0 0
3000 - Melbourne
Recruitment postcode(s) [8] 0 0
3181 - Prahran
Recruitment postcode(s) [9] 0 0
6008 - Shenton Park
Recruitment outside Australia
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United States of America
State/province [1] 0 0
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Utah
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Graz
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Stockholm
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Edirne, Istanbul
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Istanbul
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Izmir
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London, City Of
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Manchester
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Oxford

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 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.
Trial website
https://clinicaltrials.gov/show/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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
844-663-3742
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

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