Status:
TERMINATED
Safety and Tolerability Study of Mivebresib Tablet Alone or in Combination With Ruxolitinib Tablet or Navitoclax Tablet in Adult Participants With Myelofibrosis
Lead Sponsor:
AbbVie
Conditions:
Myelofibrosis (MF)
Eligibility:
All Genders
18+ years
Phase:
PHASE1
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...
Eligibility Criteria
Inclusion
- 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 myelofibrosis (PPV-MF) or post-essential thrombocytopenia myelofibrosis (PET-MF) as defined by 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 centimeters (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.
- 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):
- \>= 24 weeks duration of current ruxolitinib course, with evidence of disease that is resistant, refractory, or has lost response to ruxolitinib monotherapy;
- \< 24 weeks duration of current ruxolitinib course with documented disease progression as defined by any of the following:
- Appearance of new splenomegaly that is palpable to at least 5 centimeters (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.
- 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 teh JAKi.
Exclusion
- 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 (BCL2) and/or B-Cell Lymphoma XL (BCLXL) inhibitor, including navitoclax.
- Segment D:
- Prior exposure to JAKi and/or any BET inhibitor.
Key Trial Info
Start Date :
March 17 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 28 2023
Estimated Enrollment :
1 Patients enrolled
Trial Details
Trial ID
NCT04480086
Start Date
March 17 2021
End Date
July 28 2023
Last Update
August 29 2023
Active Locations (7)
Enter a location and click search to find clinical trials sorted by distance.
1
Stony Brook University Hospital /ID# 222653
Stony Brook, New York, United States, 11794-8183
2
UC Health - Cincinnati /ID# 224079
Cincinnati, Ohio, United States, 45267-2800
3
Thompson Cancer Survival Ctr /ID# 225802
Knoxville, Tennessee, United States, 37916
4
University of Texas MD Anderson Cancer Center /ID# 221652
Houston, Texas, United States, 77030