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
Myelofibrosis (MF)
About this trial
This is an interventional treatment trial for Myelofibrosis (MF) focused on measuring ABBV-744, Navitoclax, Ruxolitinib, ABT-263, Cancer, Myelofibrosis, MF
Eligibility Criteria
Inclusion 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 ruxolitinib 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 therapy;
< 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.
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.
Exclusion 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.
Sites / Locations
- University of California, Davis Comprehensive Cancer Center /ID# 221790
- Dartmouth-Hitchcock Medical Center /ID# 224623
- Roswell Park Comprehensive Cancer Center /ID# 222557
- The Mount Sinai Hospital /ID# 221549
- Weill Cornell Medical College /ID# 227069
- Gabrail Cancer Center Research /ID# 222802
- University of Oklahoma, Stephenson Cancer Center /ID# 224095
- Oregon Health and Science Univ /ID# 221801
- Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004
- VA Puget Sound Health Care System /ID# 224208
- Hospital Universitario Austral /ID# 228909
- Hospital Italiano de Buenos Aires /ID# 226945
- Townsville University Hospital /ID# 225859
- Royal Hobart Hospital /ID# 241677
- Royal Perth Hospital /ID# 241678
- Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636
- Hospital de Clinicas de Porto Alegre /ID# 226635
- Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein /ID# 226640
- Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 226637
- Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641
- Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 226639
- SHAT Hematologic Diseases /ID# 226007
- UMHAT Sveta Marina /ID# 226681
- Icegclinic /Id# 231086
- Fundacion Arturo Lopez Perez /ID# 225037
- Sociedad de Investigaciones Médicas Limitada /ID# 224175
- Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249
- Semmelweis Egyetem /ID# 224085
- The Chaim Sheba Medical Center /ID# 222151
- Tel Aviv Sourasky Medical Center /ID# 223548
- Hadassah Medical Center-Hebrew University /ID# 243852
- Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397
- Kyushu University Hospital /ID# 228035
- Hokkaido University Hospital /ID# 228038
- Osaka Metropolitan University Hospital /ID# 225502
- University of Yamanashi Hospital /ID# 225503
- Inje University Busan Paik Hospital /ID# 233707
- Hospital Santa Creu i Sant Pau /ID# 238501
- Hospital General Universitario Gregorio Maranon /ID# 233279
- Orebro Universitetssjukhuset /ID# 228514
- Akademiska Sjukhuset /ID# 228515
- Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 234215
- Koc Universitesi Hastanesi Translasyonel Tip Arastirma Merkezi /ID# 234214
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
Segment A: ABBV-744 Dose Identification and Optimization
Segment A: ABBV-744 Monotherapy
Segment B: Ruxolitinib + ABBV-744 "Add on" Therapy
Segment C: ABBV-744 + Navitoclax
Segment D: ABBV-744 + Ruxolitinib
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.
Participants will receive the identified safe dosing regimen of ABBV-744 as monotherapy.
Participants whose disease (myelofibrosis) is inadequately controlled by ongoing ruxolitinib therapy will receive ruxolitinib and ABBV-744 as "add-on" therapy.
Participants who have previously been exposed to JAKi, and stopped such therapy, will receive ABBV-744 and navitoclax.
Participants who have never received JAKi will receive ABBV-744 and ruxolitinib.