A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis

Phase 2

Active, not recruiting

• Conditions: Myelofibrosis (MF)
• Interventions: Drug: Navitoclax; Drug: Ruxolitinib

• Registration Number: NCT03222609
• Lead Sponsor: AbbVie

Brief Summary

This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with myelofibrosis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-17
• Study First Submitted QC: 2017-07-17
• Study First Posted: 2017-07-19
• Study Start: 2017-10-31
• Primary Completion: 2022-03-28
• Disposition First Submitted: 2023-03-01
• Disposition First Posted: 2023-03-03
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-25
• Last Update Posted: 2024-06-27
• Study Completion: 2025-01-29

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 191

Inclusion Criteria

• Participants with documented diagnosis of intermediate-2 or high-risk primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.

• Participant must be ineligible due to age, comorbidities, or unfit for unrelated or unmatched donor transplantation or unwilling to undergo stem cell transplantation at time of study entry.

• Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2.

• Prior treatment must meet at least one of the following criteria:

  • Prior or current treatment with ruxolitinib and no prior treatment with a Bromodomain and Extra-Terminal motif (BET) proteins inhibitor or another Janus Kinase 2 (JAK-2) inhibitor, and meet all of the following criteria:

    • Ruxolitinib treatment must meet at least one of the following criteria:

      • Ruxolitinib treatment for >=24 weeks with lack of efficacy defined as a lack of spleen response (refractory) or a loss of spleen or symptom response (relapsed)
      • Ruxolitinib treatment for <24 weeks with documented disease progression on spleen measurements while on ruxolitinib as defined in the protocol:
      • Ruxolitinib treatment for >=28 days with intolerance defined as new red blood cell transfusion requirement (at least 2 units/month for 2 months) while receiving a total daily ruxolitinib dose of >=30 mg but unable to reduce dose further due to lack of efficacy.

    • If receiving ruxolitinib at the time of screening, must currently be on a stable dose >=10 mg twice daily of ruxolitinib for >=4 weeks prior to the 1st dose of navitoclax.

    • Participant has at least 2 symptoms each with a score >=3 or a total score of >=12, as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days during screening prior to study drug dosing; OR

  • Prior treatment with a JAK-2 inhibitor and meet one of the following criteria:

    • Prior treatment with a JAK-2 inhibitor for at least 12 weeks
    • Prior treatment with a JAK-2 inhibitor for >=28 days complicated by either development of red blood cell transfusion requirement (at least 2 units/month for 2 months) OR Grade >= 3 adverse events of thrombocytopenia, anemia, hematoma and/or hemorrhage while on JAK-2 inhibitor treatment; OR

  • No prior treatment with a JAK-2 or BET inhibitor.

• Participant has splenomegaly as defined in the protocol.

• Participant must meet the laboratory parameters (adequate bone marrow, renal and hepatic function) as defined in the protocol.

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Exclusion Criteria

• Splenic irradiation within 6 months prior to screening, or prior splenectomy.
• Leukemic transformation (> 10% blasts in peripheral blood or bone marrow aspirate/biopsy).
• Participant is currently on medications that interfere with coagulation (including warfarin) or platelet function within 3 days prior to the first dose of study drug or during the study treatment period with the exception of low dose aspirin (up to 100 mg/day) and low-molecular-weight heparin.
• Prior therapy with a BH3 mimetic compound or stem cell transplantation.
• Participant has received strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) or moderate CYP3A inhibitors (e.g., fluconazole) within 14 days prior to the administration of the first dose of study drug.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Navitoclax	Navitoclax	Participants will be administered various doses of navitoclax once daily (QD)
Navitoclax + ruxolitinib	Ruxolitinib	Participants will be administered navitoclax once daily (QD) at various doses and a dose greater than or equal to 10 mg of ruxolitinib twice daily (BID).
Navitoclax + ruxolitinib	Navitoclax	Participants will be administered navitoclax once daily (QD) at various doses and a dose greater than or equal to 10 mg of ruxolitinib twice daily (BID).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline	From Baseline (Week 0) through Week 24	Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).

Secondary Outcome Measures

Name	Time	Method
Anemia Response	Every 12 weeks up to approximately 96 weeks	The anemia response will be assessed according to current International Working Group-Myeloproliferative Neoplasms Research and European LeukemiaNet (IWG-MRT/ELN) criteria.
Percentage of participants achieving 50% Reduction in Total System Score (TSS)	From Baseline (Week 0) through Week 24	TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0.
Change in Grade of Bone Marrow Fibrosis	Through Week 96	Bone marrow grading is assessed according to the European Consensus Grading System.

Trial Locations

Locations (91)

University of Southern California /ID# 164095; 🇺🇸 Los Angeles, California, United States

Dana-Farber Cancer Institute /ID# 162675; 🇺🇸 Boston, Massachusetts, United States

Princess Margaret Cancer Centre /ID# 214483; 🇨🇦 Toronto, Ontario, Canada

Alfred Health /ID# 215545; 🇦🇺 Melbourne, Victoria, Australia

The Kinghorn Cancer Centre /ID# 214657; 🇦🇺 Darlinghurst, New South Wales, Australia

Ascension Providence Southfield Cancer Center /ID# 223876; 🇺🇸 Southfield, Michigan, United States

University of Alberta Hospital - Division of Hematology /ID# 217698; 🇨🇦 Edmonton, Alberta, Canada

Clinical Hospital Dubrava /ID# 230504; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Long Beach Memorial Medical Ct /ID# 230148; 🇺🇸 Long Beach, California, United States

Mid Illinois Hematology & Oncology Associates, Ltd /ID# 230536; 🇺🇸 Normal, Illinois, United States

Texas Oncology- Baylor Charles A. Sammons Cancer Center /ID# 225159; 🇺🇸 Dallas, Texas, United States

Klinicka bolnica Merkur /ID# 230599; 🇭🇷 Zagreb, Grad Zagreb, Croatia

University General Hospital Attikon /ID# 230395; 🇬🇷 Athens, Attiki, Greece

University of Massachusetts - Worcester /ID# 222547; 🇺🇸 Worcester, Massachusetts, United States

MidAmerica Division, Inc. /ID# 222058; 🇺🇸 Kansas City, Missouri, United States

TOI Clinical Research /ID# 222546; 🇺🇸 Cerritos, California, United States

Semmelweis Egyetem /ID# 230518; 🇭🇺 Budapest, Hungary

ASST Spedali civili di Brescia /ID# 230420; 🇮🇹 Brescia, Italy

Galilee Medical Center /ID# 230397; 🇮🇱 Nahariya, Israel

Barwon Health /ID# 222430; 🇦🇺 Geelong, Victoria, Australia

City of Hope /ID# 221395; 🇺🇸 Duarte, California, United States

Weill Cornell Medical College /ID# 162679; 🇺🇸 New York, New York, United States

The Ohio State University /ID# 217402; 🇺🇸 Columbus, Ohio, United States

West Penn Hospital /ID# 222618; 🇺🇸 Pittsburgh, Pennsylvania, United States

Mayo Clinic /ID# 164201; 🇺🇸 Jacksonville, Florida, United States

Fiona Stanley Hospital /ID# 216809; 🇦🇺 Murdoch, Western Australia, Australia

Medical University of South Carolina /ID# 222597; 🇺🇸 Charleston, South Carolina, United States

Juntendo University Hospital /ID# 221484; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni /ID# 214900; 🇮🇹 Bergamo, Italy

Fujita Health University Hospital /ID# 221539; 🇯🇵 Toyoake-shi, Aichi, Japan

Samsung Medical Center /ID# 230381; 🇰🇷 Seoul, Korea, Republic of

Hadassah Medical Center-Hebrew University /ID# 230310; 🇮🇱 Jerusalem, Yerushalayim, Israel

CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 230718; 🇪🇸 Pamplona, Navarra, Spain

Sapporo Hokuyu Hospital /ID# 222693; 🇯🇵 Sapporo-shi, Hokkaido, Japan

Hospital del Centro Comprensivo de Cancer de la UPR /ID# 222544; 🇵🇷 San Juan, Puerto Rico

IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 230012; 🇮🇹 Bologna, Italy

Aomori Prefectural Central Hospital /ID# 221773; 🇯🇵 Aomori-shi, Aomori, Japan

Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet /ID# 230306; 🇭🇺 Budapest, Hungary

Guys and St Thomas NHS Foundation Trust /ID# 164110; 🇬🇧 London, London, City Of, United Kingdom

National Cheng Kung University Hospital /ID# 230372; 🇨🇳 Tainan, Taiwan

ASST Sette Laghi /ID# 214551; 🇮🇹 Varese, Italy

The Christie Hospital /ID# 164111; 🇬🇧 Manchester, United Kingdom

University of Yamanashi Hospital /ID# 221700; 🇯🇵 Chuo-shi, Yamanashi, Japan

Hospital Universitario Virgen de la Victoria /ID# 214709; 🇪🇸 Malaga, Spain

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 230719; 🇪🇸 Madrid, Spain

Seoul National University Hospital /ID# 230380; 🇰🇷 Seoul, Korea, Republic of

Azienda Ospedaliero Universitaria Careggi /ID# 214555; 🇮🇹 Florence, Italy

Kaohsiung Chang Gung Memorial Hospital /ID# 230371; 🇨🇳 Kaohsiung City, Kaohsiung, Taiwan

Hospital Universitario Vall d'Hebron /ID# 222415; 🇪🇸 Barcelona, Spain

Hospital Regional de Malaga /ID# 230858; 🇪🇸 Málaga, Malaga, Spain

Nippon Medical School Hospital /ID# 222692; 🇯🇵 Bunkyo-ku, Tokyo, Japan

Hospital Universitario 12 de Octubre /ID# 214710; 🇪🇸 Madrid, Spain

Belfast Health and Social Care Trust /ID# 216991; 🇬🇧 Belfast, United Kingdom

Hospital General Universitario Gregorio Maranon /ID# 214676; 🇪🇸 Madrid, Spain

General Hospital of Athens Laiko /ID# 230394; 🇬🇷 Athens, Attiki, Greece

MD Anderson Cancer Center at Texas Medical Center /ID# 162683; 🇺🇸 Houston, Texas, United States

Oncology Consultants /ID# 230930; 🇺🇸 Houston, Texas, United States

University of Texas Health San Antonio MD Anderson Cancer Center /ID# 164094; 🇺🇸 San Antonio, Texas, United States

Utah Cancer Specialists Salt Lake Clinic /ID# 222806; 🇺🇸 Salt Lake City, Utah, United States

University of Utah /ID# 164116; 🇺🇸 Salt Lake City, Utah, United States

McGill University Health Center Research Institute /ID# 223976; 🇨🇦 Montreal, Quebec, Canada

Kindai University Hospital /ID# 222689; 🇯🇵 Osakasayama-shi, Osaka, Japan

Peter MacCallum Cancer Ctr /ID# 218352; 🇦🇺 Melbourne, Victoria, Australia

UAB Comprehensive Cancer Cente /ID# 165464; 🇺🇸 Birmingham, Alabama, United States

Colorado Blood Cancer Institute /ID# 224250; 🇺🇸 Denver, Colorado, United States

Moffitt Cancer Center /ID# 164082; 🇺🇸 Tampa, Florida, United States

Henry Ford Hospital /ID# 162682; 🇺🇸 Detroit, Michigan, United States

American Oncology Partners of Maryland, PA /ID# 231299; 🇺🇸 Bethesda, Maryland, United States

Moores Cancer Center at UC San Diego /ID# 164084; 🇺🇸 La Jolla, California, United States

University of Chicago Medicine /ID# 164115; 🇺🇸 Chicago, Illinois, United States

Baptist MD Anderson Cancer Center - Jacksonville /ID# 222548; 🇺🇸 Jacksonville, Florida, United States

Indiana Blood & Marrow Transpl /ID# 165075; 🇺🇸 Indianapolis, Indiana, United States

Bend Memorial Clinic /ID# 224184; 🇺🇸 Bend, Oregon, United States

Prairie Lakes Healthcare System /ID# 224358; 🇺🇸 Watertown, South Dakota, United States

Tennessee Oncology-Nashville Centennial /ID# 221410; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology - West Texas /ID# 224784; 🇺🇸 Abilene, Texas, United States

Klinicki bolnicki centar Split /ID# 230601; 🇭🇷 Split, Splitsko-dalmatinska Zupanija, Croatia

Tel Aviv Sourasky Medical Center /ID# 230311; 🇮🇱 Tel Aviv-Yafo, Tel-Aviv, Israel

Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz Josa Andras Okta /ID# 230585; 🇭🇺 Nyiregyhaza, Szabolcs-Szatmar-Bereg, Hungary

Assuta Ashdod Medical Center /ID# 230396; 🇮🇱 Ashdod, Israel

A.O.U. Policlinico G. Rodolico S.Marco- Presidio G.Rodolico /ID# 214549; 🇮🇹 Catania, Italy

Grande Ospedale Metropolitano Bianchi Melacrino Morelli /ID# 230011; 🇮🇹 Reggio Calabria, Italy

Kyushu University Hospital /ID# 222691; 🇯🇵 Fukuoka-shi, Fukuoka, Japan

Kansai Medical University Hospital /ID# 222690; 🇯🇵 Hirakata-shi, Osaka, Japan

Dokkyo Medical University Saitama Medical Center /ID# 222332; 🇯🇵 Koshigaya-shi, Saitama, Japan

Hospital Universitario Germans Trias i Pujol /ID# 214704; 🇪🇸 Badalona, Barcelona, Spain

VA Caribbean Healthcare System /ID# 222416; 🇵🇷 San Juan, Puerto Rico

Oxford University Hospitals NHS Foundation Trust /ID# 214503; 🇬🇧 Oxford, Oxfordshire, United Kingdom

Aneurin Bevan University Health Board /ID# 230332; 🇬🇧 Newport, United Kingdom

Klinicki bolnicki centar Zagreb /ID# 230602; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 214553; 🇮🇹 Rome, Lazio, Italy