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

Trial Status: Closed to Accrual

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.

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 at least 2 symptoms each with a score >=3 or a total score of >= 12, as measured by the MFSAF v4.0 on at least 4 out of 7 days during screening prior to study drug dosing.
  • 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.

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.

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Nikolaos Papadantonakis
Phone: 205-934-0916

California

Duarte
City of Hope Comprehensive Cancer Center
Status: ACTIVE
Los Angeles
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Contact: Christine Duran
Phone: 323-865-0371
San Diego
UC San Diego Medical Center - Hillcrest
Status: CLOSED_TO_ACCRUAL

Florida

Jacksonville
Mayo Clinic in Florida
Status: CLOSED_TO_ACCRUAL
Tampa
Moffitt Cancer Center
Status: ACTIVE
Contact: Rami S. Komrokji
Phone: 813-745-4291

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: ACTIVE

Massachusetts

Boston
Brigham and Women's Hospital
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Dana-Farber Cancer Institute
Status: TEMPORARILY_CLOSED_TO_ACCRUAL

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

South Carolina

Charleston
Medical University of South Carolina
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE
San Antonio
Cancer Therapy and Research Center at The UT Health Science Center at San Antonio
Status: ADMINISTRATIVELY_COMPLETE
Contact: Sonia Lisa Creighton
Phone: 210-450-1366

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Abbvie

  • Primary ID M16-109
  • Secondary IDs NCI-2017-01899, 2017-001398-17
  • Clinicaltrials.gov ID NCT03222609