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Clinical Trials in the UK / NCT04468984
Active, not recruiting Phase 3

Study of Oral Navitoclax Tablet in Combination With Oral Ruxolitinib Tablet Versus Best Available Therapy to Assess Change in Spleen Volume in Adult Participants With Relapsed/Refractory Myelofibrosis

NCT04468984 · tracked via the Priya Life Science UK tracker
Sponsor
AbbVie
Phase
Phase 3
Started
2020-08-31
Last updated
2026-01-09

Condition(s) studied

Myelofibrosis (MF)

Investigational drug(s) / intervention(s)

NavitoclaxRuxolitinibBest Available Therapy (BAT)

Navitoclax: Tablet; Oral

Ruxolitinib: Tablet; Oral

Best Available Therapy (BAT): Tablet/Capsule; Oral or Solution for Subcutaneous Injection

Study summary

Myelofibrosis (MF) is a rare blood cancer, notable for scarring of the bone marrow (the spongy tissue inside bones) and the spleen becoming larger. The purpose of this study is to assess safety and change in spleen volume when navitoclax is given in combination with ruxolitinib, compared to best available therapy, for adult participants with MF.

Navitoclax is an investigational drug (not yet approved) being developed for the treatment of MF. Participants in this study will be randomly selected (like picking numbers out of a hat) to be in 1 of 2 treatment arms. Neither participants nor the study doctor will be able to pick which treatment arm a participants enters. In Arm A, participants will receive navitoclax in combination with ruxolitinib. In Arm B, participants will receive the best available therapy (BAT) for MF. In Arm C, participants will receive navitoclax. Adult participants with a diagnosis of MF that came back or did not get better after earlier treatment will be enrolled. Approximately 330 participants will be enrolled in approximately 322 sites across the world.

In Arm A, participants will receive navitoclax tablet by mouth once daily with by mouth ruxolitinib tablet twice daily. In Arm B, participants will receive the BAT available to the investigator. In Arm C, participants will receive navitoclax tablet by mouth once daily. Participants will receive the study drug until they experience no benefit (determined by the investigator), participants cannot tolerate the study drugs, or participants withdraw consent. The approximate treatment duration is about 3 years.

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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy volunteers
No
Inclusion Criteria: * Must complete the Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of the 7 days immediately prior to the date of randomization and must agree to collect MFSAF data daily by ePRO device during the study collection window. \-- Has at least 2 symptoms each with an average score \>= 3 or an average total score of \>= 12, as measured by the MFSAF v4.0. * Documented diagnosis of primary myelofibrosis (MF) as defined by the World Health Organization (WHO) classification, post polycythemia vera (PPV)-MF, or post essential thrombocytopenia (PET)-MF, characterized by bone marrow fibrosis grades 2 or 3. * Classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+). * Must currently be on treatment or have received prior treatment with a single Janus Kinase 2 (JAK2) inhibitor, ruxolitinib, and meet one of the following criteria (in addition to the minimum splenomegaly and symptom burden also required for eligibility): * Treatment with ruxolitinib for \>= 24 weeks that was stopped due to lack of spleen response (refractory), or loss of spleen response or symptom control after a previous response (relapsed), or was continued despite relapsed/refractory status. * Treatment with ruxolitinib for \< 24 weeks with documented disease progression while on therapy 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. * A \>= 100% increase in the palpable distance below the LCM in participants with measurable spleen distance 5 to 10 centimeters (cm) prior to the initiation of ruxolitinib. * A \>= 50% increase in the palpable distance below the LCM in participants with measurable spleen distance \> 10 cm prior to the initiation of ruxolitinib. * A spleen volume increase of \>= 25% (as assessed by Magnetic Resonance Imaging \[MRI\] or Computed Tomography \[CT\] scan) in participants with a spleen volume assessment prior to the initiation of ruxolitinib. * Prior treatment with ruxolitinib of at least 10 mg twice daily (BID) for \>= 28 days with intolerance defined as new RBC 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. Note: Participant must not require a ruxolitinib dose less than 10 mg BID (20 mg daily) due to prior history of ruxolitinibrelated ≥ Grade 3 toxicity. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Splenomegaly defined as palpable spleen measurement \>= 5 cm below left costal margin or spleen volume \>= 450 cm3 as assessed centrally by MRI or CT scan. * Baseline platelet count \>= 100 × 10\^9/L. Exclusion Criteria: * Received prior treatment with a B-cell lymphoma 2 homology 3 (BH3)-mimetic compound, bromodomain and extra-terminal (BET) inhibitor, phosphoinositide 3- kinase and telomerase inhibitors (e.g., parsaclisib), prior use of \> 1 JAK2 inhibitor or stem cell transplant. * Eligible for stem cell transplantation at the time of study entry. * Receiving medication that interferes with coagulation or platelet function within 3 days prior to the first dose of study drug or during the study treatment period except for low dose aspirin (up to 100 mg daily) and low molecular weight heparin (LMWH). * Receiving anticancer therapy for an active malignancy or MF including chemotherapy, radiation therapy, hormonal therapy such that at least 5 half-lives of that medication is completed at least 7 days prior to the first dose of study drug or within 30 days prior to first dose of study drug, whichever is shorter, and during the study treatment period (other than any overlapping therapy as part of the selected BAT).

Primary outcome measure(s)

Trial sites (229)

FacilityCityRegionStatus
Ironwood Cancer & Res Ctr /ID# 222162 Chandler Arizona
Highlands Oncology Group, PA /ID# 221826 Springdale Arkansas
City of Hope /ID# 218996 Duarte California
Providence - St. Jude Medical Center /ID# 271382 Fullerton California
Moores Cancer Center /ID# 271596 La Jolla California
Moores Cancer Center at UC San Diego /ID# 219009 La Jolla California
Long Beach Memorial Medical Ct /ID# 224542 Long Beach California
Icri /Id# 221967 Whittier California
St. Mary's Hospital Regional Cancer Center /ID# 224229 Grand Junction Colorado
Augusta University Georgia Cancer Center /ID# 219051 Augusta Georgia
Columbus Regional Research Institute /ID# 224410 Columbus Georgia
University of Chicago Medical Center /ID# 271373 Chicago Illinois
Northwest Oncology & Hematology - Elk Grove Village /ID# 222818 Elk Grove Village Illinois
Loyola University Medical Ctr /ID# 219048 Maywood Illinois
Indiana Blood & Marrow Transpl /ID# 221587 Indianapolis Indiana
Tulane Medical Center - New Orleans /ID# 222940 New Orleans Louisiana
Duplicate_Ochsner Clinic Foundation-New Orleans /ID# 222777 New Orleans Louisiana
American Oncology Partners of Maryland /ID# 222836 Bethesda Maryland
Dana-Farber Cancer Institute /ID# 218998 Boston Massachusetts
University of Michigan /ID# 218463 Ann Arbor Michigan
Henry Ford Hospital /ID# 221190 Detroit Michigan
William Beaumont Hospital /ID# 222705 Royal Oak Michigan
Saint Louis University Cancer Center /ID# 222287 St Louis Missouri
Summit Medical Group-Florham Park /ID# 222620 Florham Park New Jersey
Hackensack Univ Med Ctr /ID# 219047 Hackensack New Jersey
The Cancer Institute at St. Francis Hospital /ID# 231782 Greenvale New York
Manhattan Hematology Oncology MHO Associates /ID# 223193 New York New York
Memorial Sloan Kettering Cancer Center-Koch Center /ID# 221081 New York New York
Atrium Health Wake Forest Baptist Medical Center /ID# 222899 Winston-Salem North Carolina
MetroHealth Medical Center /ID# 222650 Cleveland Ohio
Pennsylvania Cancer Specialists & Research Institute /ID# 271376 Gettysburg Pennsylvania
Hospital of the University of Pennsylvania /ID# 219001 Philadelphia Pennsylvania
Fox Chase Cancer Center /ID# 223955 Philadelphia Pennsylvania
Texas Oncology - Abilene - Antilley Road /ID# 271379 Abilene Texas
Duplicate_Houston Methodist Hospital /ID# 223103 Houston Texas
University of Texas Health San Antonio MD Anderson Cancer Center /ID# 233942 San Antonio Texas
Utah Cancer Specialists Salt Lake Clinic /ID# 221962 Salt Lake City Utah
Virginia Cancer Specialists - Fairfax /ID# 223016 Fairfax Virginia
Providence Everett /ID# 223130 Everett Washington
Yakima Valley Memorial Hosp /ID# 224368 Yakima Washington

+ 189 more sites — see the full list on the official registry below.

On this site

📄 Jakafi (ruxolitinib) drug profile →

More AbbVie trials in the UK

Other trials for the same condition

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04468984 on ClinicalTrials.gov ↗ ← All trials in the UK