[M20-247] Safety and Tolerability Study of Oral ABBV-744 Tablet Alone or in Combination With Oral Ruxolitinib Tablet or Oral Navitoclax Tablet in Adult Participants With Myelofibrosis

JRCT ID: jRCT2031210007

Registered date:02/04/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Myelofibrosis
• Date of first enrollment: 22/03/2021
• Target sample size: 130
• Countries of recruitment: United States,Japan,Hungary,Japan,Israel,Japan,Chile,Japan
• Study type: Interventional

Intervention(s)

Segment A: ABBV-744 Dose Identification and Optimization
Participants who have been previously treated with Janus Kinase inhibitor(s) (JAKi) and stopped such therapy, will receive different dosing regimens and schedules of ABBV-744 to identify the safe dosing regimen and schedule.

Segment A: ABBV-744 Monotherapy
Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.

Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy
Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.

Segment C: ABBV-744 + Navitoclax
Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.

Segment D: ABBV-744 + Ruxolitinib
Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.

Outcome(s)

• Primary Outcome: Percentage of Participants With Adverse Events

Key inclusion & exclusion criteria

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

Include criteria

- Laboratory values indicative of adequate bone marrow, renal, and hepatic function meeting protocol criteria.
- Completion of the Myelofibrosis System Assessment Form (MFSAF) on at least 4 out of the 7 days prior to Day 1 with at least 2 symptoms with a score >=3 or a total score of >=10.
- Documented diagnosis of intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera MF (PPV-MF) or post-essential thrombocytopenia MF (PET-MF) as defined by the World Health Organization(WHO).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Intermediate - 2, or High-Risk disease as defined by the Dynamic International Prognostic Scoring System (For Segment A only, Intermediate - 1 with palpable splenomegaly >=5 centimeters [cm] below costal margin are also eligible).
- Splenomegaly defined as spleen palpation measurement >= 5 cm below costal margin or spleen volume >= 450 cubic cms as assessed by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan (for Segments A and c, baseline spleen assessment must be obtained > 7 days after discontinuation of most recent Myelofibrosis (MF) therapy. If possible, this assessment should occur within 10 days of Cycle 1 Day 1).
Segment-Specific Prior Therapy Criteria:
- Segment A:
--Prior exposure to one or more Janus Kinase inhibitors (JAKi), the most recent of which was discontinued > 28 days prior to Cycle 1, Day 1, and are intolerant, resistant, refractory or lost response to the JAKi.
- Segment B:
--Currently receiving ruxolitinib AND
--Willingness to reduce dose (if on a higher dose); and on a stable dose for 14 days or longer prior to Cycle 1 Day 1;
AND
--At least one of the following criteria (a, b, or c):
a) >= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib monotherapy;
b) < 24 weeks duration of current ruxolitinib course with documented resistance, refractories, or loss of response, 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.
--- >=100% increase in the palpable distance below the LCM, in participants with measurable spleen distance 5 -10 cm prior to the initiation of ruxolitinib.
--- >=50% increase in the palpable distance below the LCM, in participants with measurable spleen > 10 cm prior to the initiation of ruxolitinib.
---A spleen volume increase >= 25% (as assessed by MRI or CT) in participants with a spleen volume assessment available prior to the initiation of ruxolitinib.
c) Prior treatment with ruxolitinib for >= 28 days complicated by any of the following:
---Development of red blood cell transfusion requirement (at least 2 units/month for 2 months).
---Grade >= 3 adverse events of neutropenia and/or anemia while on ruxolitinib treatment, with improvement or resolution upon dose reduction.
- Segment C:
--Prior exposure to one or more JAKi (the most recent of which was discontinued > 28 days prior to Cycle 1 Day 1), and are intolerant, resistant, refractory or lost response to the JAKi.

Exclude criteria

Segment-Specific Prior Therapy Criteria:
- Segment A:
--Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors.
- Segment B:
--Prior exposure to one or more BET inhibitors.
- Segment C:
--Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL-2) and/or BCL- XL inhibitor, including navitoclax.
- Segment D:
--Prior exposure to JAKi and/or any BET inhibitor.

Related Information

• Primary Sponsor: Okubo Sumiko
• Secondary ID(s): NCT04454658