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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03222609
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	AbbVie
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	ABBVIE INC.
Principal Investigator Affiliation	AbbVie
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Belgium, Bulgaria, Canada, Croatia, France, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Poland, Puerto Rico, Russian Federation, Serbia, Spain, Taiwan, Turkey, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myelofibrosis (MF)

Arms & Interventions

Arms

Experimental: Navitoclax + 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).

Experimental: Navitoclax

Participants will be administered various doses of navitoclax once daily (QD)

Interventions

Drug: - Ruxolitinib

Tablet; Oral

Drug: - Navitoclax

Tablet; Oral

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Birmingham, Alabama

Status

Recruiting

Address

UAB Comprehensive Cancer Cente /ID# 165464

Birmingham, Alabama, 35217

Site Contact

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