ClinTrial Refer

Trial Acronym
TRANSFORM-2

Registration Number
NCT04468984

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)

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, tolerability, 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 the study at approximately 23 countries worldwide.

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.

•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 (DIPSS).

•Must have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility):
◦Prior treatment with JAK2 inhibitor 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.

◦Prior treatment with JAK2 inhibitor for < 24 weeks with documented disease progression while on JAK2 inhibitor 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 JAK2 inhibitor.
◾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 JAK2 inhibitor.
◾A >= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance > 10 cm prior to the initiation of JAK2 inhibitor.

◾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 JAK2 inhibitor.
◾Splenomegaly defined as spleen palpation measurement >= 5 cm below costal margin or spleen volume >= 450 cm3 as assessed centrally by MRI or CT scan.
◾Baseline platelet count >= 100 × 109/L.

•Received prior treatment with a BH3-mimetic compound or prior use of > 1 JAK2 inhibitor.
•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).

Trial Location Name

Address

Status

Alfred Health (Haematology)

The Alfred, Commercial Road, Melbourne VIC, Australia

Recruiting

Primary Contact : John Nguyen, john.nguyen@alfred.org.au , 03 9076 7135

Calvary Mater Newcastle Hospital (Haematology)

Edith St & Platt St, Waratah NSW 2298, Australia

Closed

Primary Contact : Kath Hall, Kathy.Hall@calvarymater.org.au , 02 4014 4891

St Vincents Hospital Sydney (Haematology)

St Vincent's Hospital Sydney, Victoria Street, Darlinghurst NSW, Australia

Closed

Primary Contact : Georgia McCaughan, georgia.mccaughan@svha.org.au , 02 9355 5656

AbbVie

Website URL

Link Name

Link URL

ANZCTR

http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=NCT04468984

Clinicaltrials.gov

https://clinicaltrials.gov/ct2/show/NCT04468984

Secondary IDs
2020-000557-27M20-178

Study Type
Interventional

Intervention Code
Treatment - Drugs

Phase
Phase 3

Minimum Age
18

Maximum Age
100

Date Registered
04/12/2020

Date Closed
N/A

Status
Open

Enrolment Type
By Specialist and/or Surgeon Referral

Mutation Status and Biomarker
Any or not stated

Is it a Cohort Trial?
No

Is this a Tele-Trial?
No

Can healthy volunteer participate?
No

Discipline

Health Condition

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