Myeloproliferative Neoplasms Clinical Trial
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) 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 see how safe and tolerable ABBV-744 is, when given alone, and in combination with ruxolitinib or navitoclax, for adult participants with MF.
ABBV-744 is an investigational drug being developed for the treatment of MF. The study has 4 segments - A, B, C, and D. In Segment A, the safe dosing regimen of ABBV-744 is identified and then, given alone as monotherapy. In Segment B, C, and D, combination therapies of ABBV-744 with either ruxolitinib or navitoclax are given. Adult participants with a diagnosis of MF will be enrolled. Around 130 participants will be enrolled in 60 sites worldwide.
In Segment A, participants will receive different doses and schedules of oral ABBV-744 tablet to identify safe dosing regimen. Additional participants will be enrolled at the identified monotherapy dosign regimen. In Segment B, participants will receive oral ruxolitinib and ABBV-744 will be given as "add-on" therapy. In Segment C, participants will receive ABBV-744 and oral navitoclax. In Segment D, participants will receive ABBV-744 and ruxolitinib. Participants will receive treatment until disease progression or the participants are not able to tolerate the study drugs.
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.
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:
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.
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.
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.
Segment-Specific Prior Therapy Criteria:
Prior exposure to one or more Bromodomain and Extra-Terminal (BET) inhibitors.
Prior exposure to one or more BET inhibitors.
Prior exposure to one or more BET inhibitors and/or any B-Cell Lymphoma 2 (BCL-2) and/or BCL- XL inhibitor, including navitoclax.
Prior exposure to JAKi and/or any BET inhibitor.
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There are 46 Locations for this study
Sacramento California, 95817, United States
Lebanon New Hampshire, 03756, United States
Buffalo New York, 14263, United States
New York New York, 10029, United States
New York New York, 10065, United States
Canton Ohio, 44718, United States
Oklahoma City Oklahoma, 73104, United States
Portland Oregon, 97239, United States
Dallas Texas, 75246, United States
Houston Texas, 77030, United States
Pilar Buenos Aires, 1629, Argentina
Ciudad Autonoma Buenos Aires Ciuadad Autonoma De Buenos Aires, 1199, Argentina
Douglas Queensland, 4814, Australia
Hobart Tasmania, 7000, Australia
Melbourne Victoria, 3000, Australia
Perth Western Australia, 6000, Australia
Goiania Goias, 74605, Brazil
Porto Alegre Rio Grande Do Sul, 90035, Brazil
São Paulo Sao Paulo, 05652, Brazil
Rio de Janeiro , 20231, Brazil
Sao Paulo , 01323, Brazil
Sao Paulo , 05403, Brazil
Sofia , 1756, Bulgaria
Varna , 9010, Bulgaria
Temuco Araucania, 48104, Chile
La Florida Region Metropolitana Santiago, 82414, Chile
Providencia Region Metropolitana Santiago, 75009, Chile
Gyongyos Heves, 3200, Hungary
Budapest , 1085, Hungary
Budapest , 1097, Hungary
Ramat Gan Tel-Aviv, 52656, Israel
Tel Aviv-Yafo Tel-Aviv, 64239, Israel
Jerusalem Yerushalayim, 91120, Israel
Milan , 20122, Italy
Fukuoka-shi Fukuoka, 812-8, Japan
Sapporo-shi Hokkaido, 060-8, Japan
Osaka-shi Osaka, 545-8, Japan
Chuo-shi Yamanashi, 409-3, Japan
Busan , 47392, Korea, Republic of
Barcelona , 08041, Spain
Madrid , 28007, Spain
Orebro Orebro Lan, 701 8, Sweden
Uppsala Uppsala Lan, 751 8, Sweden
Ankara , 06200, Turkey
Istanbul , 34010, Turkey
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