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

Myelofibrosis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Study of the PI3Kδ Inhibitor Parsaclisib Plus Ruxolitinib in Participants With Myelofibrosis Who Have Suboptimal Response to Ruxolitinib

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04816565
• Other study ID #: INCB 50465-304 /LIMBER-304
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: March 31, 2021
• Est. completion date: December 30, 2023

Study information

• Verified date: March 2021
• Source: Incyte Corporation
• Contact: Incyte Corporation Call Center (US)
• Phone: 1.855.463.3463
• Email: medinfo[@]incyte.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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 50 to < 100 × 10^9/L inclusive) and DIPSS risk category (high vs intermediate-2 vs 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 212
• Est. completion date: December 30, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (eg, danazol, hydroxyurea) 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

Related Conditions & MeSH terms

• Myelofibrosis
• Polycythemia
• Polycythemia Vera
• Post Essential Thrombocythemia Myelofibrosis
• Post Polycythemia Vera Myelofibrosis
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• parsaclisib
parsaclisib will be administered QD orally
• ruxolitinib
ruxolitinib will be administered BID orally
• placebo
placebo will be administered QD orally

Locations

Country	Name	City	State
Spain	Hospital General Universitari Vall D Hebron	Barcelona
United States	New Jersey Hematology Oncology Associates Llc	Brick	New Jersey
United States	CCARE	Fresno	California
United States	Renovatio Clinical	Houston	Texas
United States	Midamerica Cancer Care	Kansas City	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants achieving targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 24
Secondary	Proportion of participants who have a targeted reduction in Total Symptom Score (TSS)	Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Change in TSS	Change in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Time to the first = 50% reduction in TSS	Reduction in TSS is measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.	Baseline to Week 24
Secondary	Overall Survival (OS)	OS is defined as randomization date to death due to any cause	Up to approximately 36 months
Secondary	Number of Treatment Emergent Adverse Events (TEAE)	Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug up to 35 days after last dose of study drug.	Up to approximately 36 months
Secondary	Time of onset of targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 108
Secondary	Duration of maintenance of targeted reduction in spleen volume	Reduction in spleen volume is measured by Magnetic Resonance Imaging (MRI) or Computed Tomography (CT).	Baseline to Week 108