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

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 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.

View Eligibility Criteria

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.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

130

Study ID:

NCT04454658

Recruitment Status:

Recruiting

Sponsor:

AbbVie

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There are 46 Locations for this study

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University of California, Davis Comprehensive Cancer Center /ID# 221790
Sacramento California, 95817, United States
Dartmouth-Hitchcock Medical Center /ID# 224623
Lebanon New Hampshire, 03756, United States
Roswell Park Comprehensive Cancer Center /ID# 222557
Buffalo New York, 14263, United States
The Mount Sinai Hospital /ID# 221549
New York New York, 10029, United States
Weill Cornell Medical College /ID# 227069
New York New York, 10065, United States
Gabrail Cancer Center Research /ID# 222802
Canton Ohio, 44718, United States
University of Oklahoma, Stephenson Cancer Center /ID# 224095
Oklahoma City Oklahoma, 73104, United States
Oregon Health and Science Univ /ID# 221801
Portland Oregon, 97239, United States
Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 240004
Dallas Texas, 75246, United States
University of Texas MD Anderson Cancer Center /ID# 221651
Houston Texas, 77030, United States
VA Puget Sound Health Care System /ID# 224208
Seattle Washington, 98108, United States More Info
Site Coordinator
Contact
844-663-3742
Hospital Universitario Austral /ID# 228909
Pilar Buenos Aires, 1629, Argentina
Hospital Italiano de Buenos Aires /ID# 226945
Ciudad Autonoma Buenos Aires Ciuadad Autonoma De Buenos Aires, 1199, Argentina
Townsville University Hospital /ID# 225859
Douglas Queensland, 4814, Australia
Royal Hobart Hospital /ID# 241677
Hobart Tasmania, 7000, Australia
Peter MacCallum Cancer Ctr /ID# 224718
Melbourne Victoria, 3000, Australia
Royal Perth Hospital /ID# 241678
Perth Western Australia, 6000, Australia
Hospital das Clinicas da Universidade Federal de Goiás /ID# 226636
Goiania Goias, 74605, Brazil
Hospital de Clinicas de Porto Alegre /ID# 226635
Porto Alegre Rio Grande Do Sul, 90035, Brazil
Sociedade Beneficente Israelita Hospital Albert Einstein /ID# 226640
São Paulo Sao Paulo, 05652, Brazil
Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) /ID# 226637
Rio de Janeiro , 20231, Brazil
Real e Benemérita Associação Portuguesa de Beneficência /ID# 226641
Sao Paulo , 01323, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo /ID# 226639
Sao Paulo , 05403, Brazil
SHAT Hematologic Diseases /ID# 226007
Sofia , 1756, Bulgaria
UMHAT Sveta Marina /ID# 226681
Varna , 9010, Bulgaria
Sociedad de Investigaciones Medicas /ID# 224175
Temuco Araucania, 48104, Chile
Icegclinic /Id# 231086
La Florida Region Metropolitana Santiago, 82414, Chile
Fundacion Arturo Lopez Perez /ID# 225037
Providencia Region Metropolitana Santiago, 75009, Chile
Clinexpert Kft. Fazis I Vizsgalohely /ID# 242249
Gyongyos Heves, 3200, Hungary
Semmelweis Egyetem /ID# 224085
Budapest , 1085, Hungary
Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 240965
Budapest , 1097, Hungary
The Chaim Sheba Medical Center /ID# 222151
Ramat Gan Tel-Aviv, 52656, Israel
Tel Aviv Sourasky Medical Center /ID# 223548
Tel Aviv-Yafo Tel-Aviv, 64239, Israel
Hadassah Medical Center-Hebrew University /ID# 243852
Jerusalem Yerushalayim, 91120, Israel
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244397
Milan , 20122, Italy
Kyushu University Hospital /ID# 228035
Fukuoka-shi Fukuoka, 812-8, Japan
Hokkaido University Hospital /ID# 228038
Sapporo-shi Hokkaido, 060-8, Japan
Osaka Metropolitan University Hospital /ID# 225502
Osaka-shi Osaka, 545-8, Japan
University of Yamanashi Hospital /ID# 225503
Chuo-shi Yamanashi, 409-3, Japan
Inje University Busan Paik Hospital /ID# 233707
Busan , 47392, Korea, Republic of
Hospital Santa Creu i Sant Pau /ID# 238501
Barcelona , 08041, Spain
Hospital General Universitario Gregorio Maranon /ID# 233279
Madrid , 28007, Spain
Orebro Universitetssjukhuset /ID# 228514
Orebro Orebro Lan, 701 8, Sweden
Akademiska Sjukhuset /ID# 228515
Uppsala Uppsala Lan, 751 8, Sweden
Dr. Abdurrahman Yurtaslan Ankara Onkoloji Egitim ve Arastirma Hastanesi /ID# 234215
Ankara , 06200, Turkey
Koc Universitesi Hastanesi Translasyonel Tip Arastirma Merkezi /ID# 234214
Istanbul , 34010, Turkey

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

130

Study ID:

NCT04454658

Recruitment Status:

Recruiting

Sponsor:


AbbVie

How clear is this clinincal trial information?

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