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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04468984
Ethics application status
Date submitted
10/07/2020
Date registered
13/07/2020
Date last updated
1/04/2021

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) - 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 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 Short Form (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 achieved 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 - Overall survival is defined as the time from start of study to the date of death from any cause.
Timepoint [7] 0 0
Up to approximately 3 years
Secondary outcome [8] 0 0
Leukemia-Free Survival - Leukemia free survival is the time from start of study to the date of development of leukemia.
Timepoint [8] 0 0
Up to approximately 3 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
- Must be able to complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at
least 4 out of 7 days prior to randomization.

-- Has at least 2 symptoms with a score >= 3 or a total score of >= 12, as measured by
the MFSAF v4.0.

- Documented diagnosis of primary myelofibrosis (MF), post polycythemia vera (PPV)-MF,
or post essential thrombocytopenia (PET)-MF as defined by the World Health
Organization (WHO) classification.

- 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 loss 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 or current treatment with ruxolitinib 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.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

- Splenomegaly defined as palpable spleen measurement >= 5 cm below 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
Gender
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.

- Eligible for allogeneic stem cell transplantation at the time of study entry.

- Receiving medication that interferes with coagulation or platelet function except for
low dose aspirin (up to 100 milligrams daily) and low molecular weight heparin (LMWH)
within 3 days prior to the first dose of study drug or during the study treatment
period.

- Receiving anticancer therapy including chemotherapy, radiation therapy, hormonal
therapy (with the exception of hormones for thyroid conditions or estrogen replacement
therapy) within 30 days prior to first dose of study drug, 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
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
Border Medical Oncology Research Unit Albury Wodonga Regional Cancer Centre /ID# 223848 - Albury
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre /ID# 221097 - Darlinghurst
Recruitment hospital [3] 0 0
The Tweed Hospital /ID# 224212 - Tweed Heads
Recruitment hospital [4] 0 0
Calvary Mater Newcastle /ID# 224324 - Waratah
Recruitment hospital [5] 0 0
The Alfred Hospital /ID# 221096 - Prahran
Recruitment hospital [6] 0 0
Royal Perth Hospital /ID# 221099 - Shenton Park
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [4] 0 0
2298 - Waratah
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3181 - Prahran
Recruitment postcode(s) [6] 0 0
6008 - Shenton Park
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04468984
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/NCT04468984