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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04468984




Registration number
NCT04468984
Ethics application status
Date submitted
10/07/2020
Date registered
13/07/2020

Titles & IDs
Public title
Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis
Scientific 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)
Secondary ID [1] 0 0
2020-000557-27
Secondary ID [2] 0 0
M20-178
Universal Trial Number (UTN)
Trial acronym
TRANSFORM-2
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 - Best Available Therapy (BAT)

Experimental: Arm A: Navitoclax + Ruxolitinib - Participants will receive navitoclax tablets once daily and ruxolitinib tablets twice daily.

Active comparator: Arm B: Best Available Therapy (BAT) - Participants will receive one of the BAT options, per the investigator's discretion.


Treatment: Drugs: Navitoclax
Tablet; Oral

Treatment: Drugs: Ruxolitinib
Tablet; Oral

Treatment: Drugs: Best Available Therapy (BAT)
Tablet/Capsule; Oral or Solution for Subcutaneous Injection

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
Percentage of Participants who achieve at least 50% Reduction 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% at any time
Timepoint [2] 0 0
Baseline (Week 0) Up to Week 97
Secondary outcome [3] 0 0
Percentage of Participants with Reduction in Grade of Bone Marrow Fibrosis
Timepoint [3] 0 0
Baseline (Week 0) Up to Week 97
Secondary outcome [4] 0 0
Percentage of Participants with Anemia Response
Timepoint [4] 0 0
Baseline (Week 0) Up to Week 97
Secondary outcome [5] 0 0
Percentage of Participants with Overall Survival
Timepoint [5] 0 0
Last Visit Up to 5 Years
Secondary outcome [6] 0 0
Percentage of Participants with Leukemia-free Survival
Timepoint [6] 0 0
Last Visit Up to 5 Years
Secondary outcome [7] 0 0
Percentage of Participants with Change in Fatigue
Timepoint [7] 0 0
Baseline (Week 0) Up to Week 24
Secondary outcome [8] 0 0
Time to Deterioration of Physical Functioning
Timepoint [8] 0 0
Baseline (Week 0) Up to Week 97
Secondary outcome [9] 0 0
Percentage of Participants with at Least 50% Reduction in TSS
Timepoint [9] 0 0
Baseline (Week 0) Up to Week 97

Eligibility
Key inclusion criteria
* Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window.

-- Has at least 2 symptoms each with an average score >= 3 or an average total score of >= 12, as measured by the MFSAF v4.0.
* Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3.
* Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+).
* Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):

* Treatment with ruxolitinib for >= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status.
* Treatment with ruxolitinib for < 24 weeks with documented disease progression while on therapy as defined by any of the following:

* Appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in participants with no evidence of splenomegaly prior to the initiation of ruxolitinib.
* A >= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib.
* A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of ruxolitinib.
* A spleen volume increase of >= 25% (as assessed by Magnetic Resonance Imaging [MRI] or Computed Tomography [CT] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib.
* Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for >= 28 days with intolerance defined as new RBC transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >= 30 mg but unable to reduce dose further due to lack of efficacy.

Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated = Grade 3 toxicity.

* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
* Splenomegaly defined as palpable spleen measurement >= 5 cm below left costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
* Baseline platelet count >= 100 × 10^9/L.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Received prior treatment with a BH3-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, or prior use of > 1 JAK2 inhibitor or stem cell transplant.
* Eligible for stem cell transplantation at the time of study entry.
* 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 mg daily) and low molecular weight heparin (LMWH).
* Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

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
Open (masking not used)
Who is / are masked / blinded?



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
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,VIC,WA
Recruitment hospital [1] 0 0
The Kinghorn Cancer Centre /ID# 221097 - Darlinghurst
Recruitment hospital [2] 0 0
Border Medical Oncology Research Unit Albury Wodonga Regiona /ID# 223848 - East Albury
Recruitment hospital [3] 0 0
Calvary Mater Newcastle /ID# 224324 - Waratah
Recruitment hospital [4] 0 0
The Alfred Hospital /ID# 221096 - Melbourne
Recruitment hospital [5] 0 0
Royal Perth Hospital /ID# 221099 - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2640 - East Albury
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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Indiana
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Massachusetts
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Michigan
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New Jersey
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New York
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Napoli
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Reggio Calabria
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Udine
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Italy
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Vicenza
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Aomori
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Chiba
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Ehime
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Iwate
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Mie
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Tokyo
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Yamanashi
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Seoul Teugbyeolsi
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Katowice
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Puerto Rico
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San Juan
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Russian Federation
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Moskva
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Russian Federation
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Moscow
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Russian Federation
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Sankt-Peterburg
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Russian Federation
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Tula
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Serbia
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Beograd
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Serbia
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Novi Sad
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South Africa
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Gauteng
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Spain
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A Coruna
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Spain
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Asturias
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Barcelona
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Spain
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Las Palmas
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Spain
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Granada
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Spain
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Madrid
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Spain
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Malaga
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Salamanca
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Sevilla
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Spain
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Valencia
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Sweden
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Skane Lan
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Switzerland
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Basel-Stadt
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Switzerland
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Bern
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Taiwan
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Kaohsiung
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Taichung
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Taoyuan City
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Turkey
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Ankara
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Turkey
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Edirne, Istanbul
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Izmir
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Mersin
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Samsun
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United Kingdom
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Lincolnshire
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London, City Of
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Norfolk
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Birmingham
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Edinburgh
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Newcastle upon Tyne

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Clinical study report (CSR)
When will data be available (start and end dates)?
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Available to whom?
To learn more about the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/abbvie/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.