[M20-178] Myelofibrosis: Phase 3 Study of Navitoclax Plus Ruxolitinib Versus Best Available Therapy

JRCT ID: jRCT2011210016

Registered date:09/06/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Myelofibrosis
• Date of first enrollment: 03/08/2021
• Target sample size: 23
• Countries of recruitment: Australia,Japan,Austria,Japan,Belgium,Japan,Canada,Japan,France,Japan,Germany,Japan,Israel,Japan,Italy,Japan,Netherlands,Japan,Russia,Japan,Korea,Japan,Spain,Japan,Sweden,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Experimental: Arm A: Navitoclax + Ruxolitinib
- Participants will receive Navitoclax in combination with Ruxolitinib
Active Comparator: Placebo for Navitoclax + Ruxolitinib
- Participants will receive placebo for Navitoclax and Ruxolitinib

Outcome(s)

• Primary Outcome: Percentage of Participants who achieve Spleen Volume Reduction of at least 35% at Week 24 (SVR35W24)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Must complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days 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 World Health Organization (WHO) classification, Post polycythemia vera (PPV) - MF or Post Essential Thrombocytopenia (PET) - MF.
- 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 ruxolitinib related >= Grade 3 toxicity.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Splenomegaly defined as spleen palpation measurement >= 5 centimeters (cm) below left costal margin or spleen volume greater than or equal to 450 cubic cm as assessed centrally by MRI or CT scan.
- Baseline platelet count >= 100 x 10^9/L.

Exclude 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).

Related Information

• Primary Sponsor: Okubo Sumiko
• Secondary ID(s): NCT04468984