To Evaluate Efficacy and Safety of Parsaclisib and Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (LIMBER-304)

Study Purpose

The purpose of the study is to compare the efficacy and safety of parsaclisib when combined with ruxolitinb versus placebo combined with ruxolitinib in participants with myelofibrosis who have suboptimal response while receiving ruxolitinib monotherapy.

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:

- Diagnosis of PMF, PPV-MF, or PET-MF.

- DIPSS risk category of intermediate-1, intermediate-2, or high.

- Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1.

- Palpable spleen of ≥ 5 cm below the left costal margin on physical examination at the screening visit.

- Active symptoms of MF at the screening visit, as demonstrated by the presence of a TSS of ≥ 10 using the Screening Symptom Form.

- Participants with an ECOG performance status score of 0, 1, or 2.

- Screening bone marrow biopsy specimen and pathology report(s) available that was obtained within the prior 2 months or willingness to undergo a bone marrow biopsy at screening/baseline; willingness to undergo bone marrow biopsy at Week 24 and every 24 weeks there after.

Screening/baseline biopsy specimen must show diagnosis of MF.

- Life expectancy of at least 24 weeks.

- Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

- Prior therapy with any drug that inhibits PI3K (examples of drugs targeting this pathway include but are not limited to INCB040093, idelalisib, duvelisib, buparlisib, copanlisib, and umbralisib).

- Use of experimental drug therapy for MF or any other standard drug used for MF (whether for treatment of MF or another indication) with the exception of ruxolitinib, within 3 months of starting study drug, and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better.

- Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.

- Recent history of inadequate bone marrow reserve.

- Inadequate liver and renal function at screening.

- Active bacterial, fungal, parasitic, or viral infection that requires therapy.

- Active HBV or HCV infection that requires treatment or at risk for HBV reactivation.

- Known HIV infection.

- Uncontrolled, severe, or unstable cardiac disease that in the investigator's opinion may jeopardize the safety of the participant or compliance with the Protocol.

- Active invasive malignancy over the previous 2 years.

- Splenic irradiation within 6 months before receiving the first dose of study drug.

- Concurrent use of any prohibited medications.

- Active alcohol or drug addiction that would interfere with the ability to comply with the study requirements.

- Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half lives(whichever is longer) before the first dose of study drug or anticipated during the study.

- Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.

- Currently breastfeeding or pregnant.

- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.

- History of Grade 3 or 4 irAEs from prior immunotherapy.

- Receipt of any live vaccine within 30 days of the first dose of study drug.

- Unwillingness to receive RBC transfusions to treat low hemoglobin levels.

- Known hypersensitivity or severe reaction to parsaclisib or ruxolitinib or excipients of parsaclisib/matching placebo or ruxolitinib formulations.

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.	NCT04551053
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 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Incyte Corporation
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Albert Assad, M.D.
Principal Investigator Affiliation	Incyte Corporation
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Austria, Belgium, China, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Romania, Spain, Taiwan, Turkey, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Myelofibrosis, Primary Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Post Polycythemia Vera Myelofibrosis
Study Website:	View Trial Website

Additional Details

Prospective participants must be on stable doses of ruxolitinib ranging from 5 mg BID to 25 mg BID and will have been on that dose for at least the last 8 weeks prior to Day 1. At least 3 months duration of prior ruxolitinib is required. Participants must meet Protocol-defined criteria for suboptimal response to ruxolitinib monotherapy. After participants have been determined to be eligible for the study and completed the baseline symptom diary assessment for 7 days, they will be randomized to 1 of 2 treatment groups, with stratification for platelet count (≥ 100 × 10^9/L vs.#46;50 to < 100 × 10^9/L inclusive) and DIPSS risk category (high vs.#46;intermediate-2 vs.#46;intermediate-1). Once a participant has completed the week 24 assessments, the participant's treatment assignment will then be unblinded and if found to be placebo, the participant will have the opportunity to crossover to begin receiving parsaclisib, together with continued ruxolitinib, as long as hematology parameters are adequate.

Arms & Interventions

Arms

Experimental: Group A : ruxolitinib +parsaclisib

Participants will receive parsaclisib starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.

Placebo Comparator: Group B : ruxolitinib + placebo

Participants will receive placebo starting from Day 1 for the duration of study, while continuing to receive the stable dose of ruxolitinib they were taking for the 8 weeks prior to Day 1.

Interventions

Drug: - parsaclisib

parsaclisib will be administered QD orally

Drug: - ruxolitinib

ruxolitinib will be administered BID orally

Drug: - placebo

placebo will be administered QD orally

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.

Berkeley, California

Status

Recruiting

Address

Sutter Health Alta Bates Summit Medical Center Absmc Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, 94704

Site Contact

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