Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04468984




Registration number
NCT04468984
Ethics application status
Date submitted
10/07/2020
Date registered
13/07/2020
Date last updated
23/05/2024

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
31/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/11/2031
Actual
Sample size
Target
Accrual to date
Final
295
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Austria
State/province [23] 0 0
Niederoesterreich
Country [24] 0 0
Austria
State/province [24] 0 0
Oberoesterreich
Country [25] 0 0
Austria
State/province [25] 0 0
Steiermark
Country [26] 0 0
Austria
State/province [26] 0 0
Wien
Country [27] 0 0
Belgium
State/province [27] 0 0
Antwerpen
Country [28] 0 0
Belgium
State/province [28] 0 0
Bruxelles-Capitale
Country [29] 0 0
Belgium
State/province [29] 0 0
Hainaut
Country [30] 0 0
Belgium
State/province [30] 0 0
Oost-Vlaanderen
Country [31] 0 0
Belgium
State/province [31] 0 0
West-Vlaanderen
Country [32] 0 0
Belgium
State/province [32] 0 0
Sint-Niklaas
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Sofia
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Pleven
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Varna
Country [36] 0 0
Canada
State/province [36] 0 0
Ontario
Country [37] 0 0
Canada
State/province [37] 0 0
Quebec
Country [38] 0 0
Croatia
State/province [38] 0 0
Grad Zagreb
Country [39] 0 0
Croatia
State/province [39] 0 0
Splitsko-dalmatinska Zupanija
Country [40] 0 0
Croatia
State/province [40] 0 0
Osijek
Country [41] 0 0
Czechia
State/province [41] 0 0
Brno
Country [42] 0 0
Czechia
State/province [42] 0 0
Praha
Country [43] 0 0
Denmark
State/province [43] 0 0
Nordjylland
Country [44] 0 0
Denmark
State/province [44] 0 0
Sjælland
Country [45] 0 0
France
State/province [45] 0 0
Alpes-Maritimes
Country [46] 0 0
France
State/province [46] 0 0
Gard
Country [47] 0 0
France
State/province [47] 0 0
Gironde
Country [48] 0 0
France
State/province [48] 0 0
Ile-de-France
Country [49] 0 0
France
State/province [49] 0 0
Pays-de-la-Loire
Country [50] 0 0
France
State/province [50] 0 0
Rhone
Country [51] 0 0
France
State/province [51] 0 0
Savoie
Country [52] 0 0
France
State/province [52] 0 0
Angers
Country [53] 0 0
France
State/province [53] 0 0
Paris
Country [54] 0 0
Germany
State/province [54] 0 0
Baden-Wuerttemberg
Country [55] 0 0
Germany
State/province [55] 0 0
Bayern
Country [56] 0 0
Germany
State/province [56] 0 0
Sachsen
Country [57] 0 0
Germany
State/province [57] 0 0
Bochum
Country [58] 0 0
Germany
State/province [58] 0 0
Chemnitz
Country [59] 0 0
Germany
State/province [59] 0 0
Hamburg
Country [60] 0 0
Germany
State/province [60] 0 0
Munich
Country [61] 0 0
Germany
State/province [61] 0 0
Rostock
Country [62] 0 0
Greece
State/province [62] 0 0
Achaia
Country [63] 0 0
Greece
State/province [63] 0 0
Attiki
Country [64] 0 0
Greece
State/province [64] 0 0
Athens
Country [65] 0 0
Greece
State/province [65] 0 0
RION Patras Achaia
Country [66] 0 0
Greece
State/province [66] 0 0
Thessaloniki
Country [67] 0 0
Hungary
State/province [67] 0 0
Fejer
Country [68] 0 0
Hungary
State/province [68] 0 0
Hajdu-Bihar
Country [69] 0 0
Hungary
State/province [69] 0 0
Somogy
Country [70] 0 0
Hungary
State/province [70] 0 0
Szabolcs-Szatmar-Bereg
Country [71] 0 0
Hungary
State/province [71] 0 0
Szeged
Country [72] 0 0
Israel
State/province [72] 0 0
H_efa
Country [73] 0 0
Israel
State/province [73] 0 0
HaDarom
Country [74] 0 0
Israel
State/province [74] 0 0
HaMerkaz
Country [75] 0 0
Israel
State/province [75] 0 0
HaTsafon
Country [76] 0 0
Israel
State/province [76] 0 0
Tel-Aviv
Country [77] 0 0
Israel
State/province [77] 0 0
Yerushalayim
Country [78] 0 0
Israel
State/province [78] 0 0
Haifa
Country [79] 0 0
Italy
State/province [79] 0 0
Ancona
Country [80] 0 0
Italy
State/province [80] 0 0
Lazio
Country [81] 0 0
Italy
State/province [81] 0 0
Monza E Brianza
Country [82] 0 0
Italy
State/province [82] 0 0
Piemonte
Country [83] 0 0
Italy
State/province [83] 0 0
Roma
Country [84] 0 0
Italy
State/province [84] 0 0
Bergamo
Country [85] 0 0
Italy
State/province [85] 0 0
Bologna
Country [86] 0 0
Italy
State/province [86] 0 0
Catania
Country [87] 0 0
Italy
State/province [87] 0 0
Florence
Country [88] 0 0
Italy
State/province [88] 0 0
Napoli
Country [89] 0 0
Italy
State/province [89] 0 0
Palermo
Country [90] 0 0
Italy
State/province [90] 0 0
Reggio Calabria
Country [91] 0 0
Italy
State/province [91] 0 0
Udine
Country [92] 0 0
Italy
State/province [92] 0 0
Varese
Country [93] 0 0
Italy
State/province [93] 0 0
Vicenza
Country [94] 0 0
Japan
State/province [94] 0 0
Aichi
Country [95] 0 0
Japan
State/province [95] 0 0
Aomori
Country [96] 0 0
Japan
State/province [96] 0 0
Chiba
Country [97] 0 0
Japan
State/province [97] 0 0
Ehime
Country [98] 0 0
Japan
State/province [98] 0 0
Fukuoka
Country [99] 0 0
Japan
State/province [99] 0 0
Fukushima
Country [100] 0 0
Japan
State/province [100] 0 0
Gifu
Country [101] 0 0
Japan
State/province [101] 0 0
Hokkaido
Country [102] 0 0
Japan
State/province [102] 0 0
Hyogo
Country [103] 0 0
Japan
State/province [103] 0 0
Ishikawa
Country [104] 0 0
Japan
State/province [104] 0 0
Iwate
Country [105] 0 0
Japan
State/province [105] 0 0
Kanagawa
Country [106] 0 0
Japan
State/province [106] 0 0
Kumamoto
Country [107] 0 0
Japan
State/province [107] 0 0
Kyoto
Country [108] 0 0
Japan
State/province [108] 0 0
Mie
Country [109] 0 0
Japan
State/province [109] 0 0
Miyazaki
Country [110] 0 0
Japan
State/province [110] 0 0
Niigata
Country [111] 0 0
Japan
State/province [111] 0 0
Okayama
Country [112] 0 0
Japan
State/province [112] 0 0
Osaka
Country [113] 0 0
Japan
State/province [113] 0 0
Saitama
Country [114] 0 0
Japan
State/province [114] 0 0
Shizuoka
Country [115] 0 0
Japan
State/province [115] 0 0
Tokyo
Country [116] 0 0
Japan
State/province [116] 0 0
Yamanashi
Country [117] 0 0
Korea, Republic of
State/province [117] 0 0
Gyeonggido
Country [118] 0 0
Korea, Republic of
State/province [118] 0 0
Seoul Teugbyeolsi
Country [119] 0 0
Korea, Republic of
State/province [119] 0 0
Busan
Country [120] 0 0
Korea, Republic of
State/province [120] 0 0
Seoul
Country [121] 0 0
New Zealand
State/province [121] 0 0
Auckland
Country [122] 0 0
Poland
State/province [122] 0 0
Lodzkie
Country [123] 0 0
Poland
State/province [123] 0 0
Lubelskie
Country [124] 0 0
Poland
State/province [124] 0 0
Malopolskie
Country [125] 0 0
Poland
State/province [125] 0 0
Mazowieckie
Country [126] 0 0
Poland
State/province [126] 0 0
Pomorskie
Country [127] 0 0
Poland
State/province [127] 0 0
Wielkopolskie
Country [128] 0 0
Poland
State/province [128] 0 0
Katowice
Country [129] 0 0
Puerto Rico
State/province [129] 0 0
San Juan
Country [130] 0 0
Russian Federation
State/province [130] 0 0
Moskva
Country [131] 0 0
Russian Federation
State/province [131] 0 0
Moscow
Country [132] 0 0
Russian Federation
State/province [132] 0 0
Sankt-Peterburg
Country [133] 0 0
Russian Federation
State/province [133] 0 0
Tula
Country [134] 0 0
Serbia
State/province [134] 0 0
Beograd
Country [135] 0 0
Serbia
State/province [135] 0 0
Novi Sad
Country [136] 0 0
South Africa
State/province [136] 0 0
Gauteng
Country [137] 0 0
Spain
State/province [137] 0 0
A Coruna
Country [138] 0 0
Spain
State/province [138] 0 0
Asturias
Country [139] 0 0
Spain
State/province [139] 0 0
Barcelona
Country [140] 0 0
Spain
State/province [140] 0 0
Las Palmas
Country [141] 0 0
Spain
State/province [141] 0 0
Granada
Country [142] 0 0
Spain
State/province [142] 0 0
Madrid
Country [143] 0 0
Spain
State/province [143] 0 0
Malaga
Country [144] 0 0
Spain
State/province [144] 0 0
Salamanca
Country [145] 0 0
Spain
State/province [145] 0 0
Sevilla
Country [146] 0 0
Spain
State/province [146] 0 0
Valencia
Country [147] 0 0
Sweden
State/province [147] 0 0
Skane Lan
Country [148] 0 0
Switzerland
State/province [148] 0 0
Basel-Stadt
Country [149] 0 0
Switzerland
State/province [149] 0 0
Bern
Country [150] 0 0
Taiwan
State/province [150] 0 0
Kaohsiung
Country [151] 0 0
Taiwan
State/province [151] 0 0
Taichung
Country [152] 0 0
Taiwan
State/province [152] 0 0
Tainan City
Country [153] 0 0
Taiwan
State/province [153] 0 0
Taipei
Country [154] 0 0
Taiwan
State/province [154] 0 0
Taoyuan City
Country [155] 0 0
Turkey
State/province [155] 0 0
Ankara
Country [156] 0 0
Turkey
State/province [156] 0 0
Edirne, Istanbul
Country [157] 0 0
Turkey
State/province [157] 0 0
Izmir
Country [158] 0 0
Turkey
State/province [158] 0 0
Mersin
Country [159] 0 0
Turkey
State/province [159] 0 0
Samsun
Country [160] 0 0
United Kingdom
State/province [160] 0 0
Lincolnshire
Country [161] 0 0
United Kingdom
State/province [161] 0 0
London, City Of
Country [162] 0 0
United Kingdom
State/province [162] 0 0
Norfolk
Country [163] 0 0
United Kingdom
State/province [163] 0 0
Birmingham
Country [164] 0 0
United Kingdom
State/province [164] 0 0
Edinburgh
Country [165] 0 0
United Kingdom
State/province [165] 0 0
Newcastle upon Tyne

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

Ethics approval
Ethics application status

Summary
Brief summary
Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the
spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to
assess safety and change in spleen volume when navitoclax is given in combination with
ruxolitinib, 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. Participants in this study will be randomly selected (like picking numbers out of a hat)
to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to
pick which treatment arm a participants enters. 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 MF that came back or
did not get better after earlier treatment will be enrolled. Approximately 330 participants
will be enrolled in approximately 210 sites across the world.

In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth
ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the
investigator. Participants will receive the study drug until they experience no benefit
(determined by the investigator), 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/ct2/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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries