A Study of Ruxolitinib in Combination With Abemaciclib for the Treatment of Myelofibrosis

NCT05714072 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 22-075
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

The study is being done to see if the combination of ruxolitinib and abemaciclib is a safe and effective treatment for people with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.

Conditions

Myelofibrosis Due to and Following Polycythemia Vera

Keywords

Ruxolitinib; Abemaciclib; 22-075

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with dose-limiting toxicity (DLT)

  Dose-limiting toxicities (DLTs) will be defined based on toxicities observed during the first cycle of the combination treatment. Adverse events (AEs) that are possibly, probably or definitely related to study drug(s) will be scored as toxicities. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  28 days

Secondary Outcomes (1)

• overall response rate (ORR)

  2 years

Study Arms (1)

Ruxolitinib plus Abemaciclib

EXPERIMENTAL

This will be a phase 1 study with a traditional "3+3" design of combination ruxolitinib (at fixed doses of 10mg BID or 15mg BID) and abemaciclib. There are 3 planned dose levels of abemaciclib: 50, 100 and 150 mg. Cycles will be 4 weeks (28 days) long and DLT window will consist of first cycle.

Drug: Ruxolitinib; Drug: Abemaciclib

Interventions

Ruxolitinib DRUG

10mg BID or 15mg BID

Ruxolitinib plus Abemaciclib

Abemaciclib DRUG

50, 100 and 150 mg

Ruxolitinib plus Abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with PMF or post-PV/ET MF requiring therapy and intermediate-1, -2 or high risk disease by the Dynamic International Prognostic Scoring System (DIPSS) , DIPSS-plus MIPSS7021 or MIPSS70-plus v2.0 if PMF and by the Myelofibrosis Secondary to PV and ET - Prognostic Model (MYSEC-PM) if post-PV/ET MF
• Treated with ruxolitinib for ≥12 weeks with a stable dose for the preceding ≥4 weeks. Patients must be on a dose of ruxolitinib of 10mg or 15mg BID at the time of screening.
• Evidence of inadequate response to ruxolitinib: Patients must have palpable splenomegaly ≥5 cm below the left costal margin at study entry AND/OR active MPN symptoms, as defined by the presence of one symptom score ≥5 or two symptom scores ≥3 using the screening symptom form
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2.
• Life expectancy of at least 24 weeks.
• The patient has adequate organ function for all of the following criteria:
• ° Hematologic
• ANC ≥1.5 × 10\^9/L
• Platelets ≥75 × 10\^9/L
• Hepatic
• Total bilirubin ≤1.5 × ULN
• Patients with Gilbert's syndrome with a total bilirubin \>2.0 times ULN and direct bilirubin within normal limits are permitted.
• ALT and AST ≤3 × ULN
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to start of therapy. A washout period of at least 21 days is required between last chemotherapy dose and start of combination therapy (with the exception of hydroxyurea, which may be continued until the day before dosing begins). Patients should not receive hydroxyurea while on treatment.

You may not qualify if:

• Prior therapy with CDK4/6 inhibitors.
• The patient has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to randomization, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study.
• Concomitant treatment with other investigational agents for therapy of MF
• Splenic irradiation within the 4 months preceding study treatment initiation.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Patients with active CNS leukemia.
• Inability to swallow pills or GI conditions that would be expected to impair intestinal absorption.
• History of allergic reactions attributed to ruxolitinib, abemaciclib or compounds of similar chemical or biologic composition.
• The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Patients with ≥ 10% circulating or bone marrow blasts.
• Pregnancy and lactation.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A that cannot be discontinued. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts such as the Physicians' Desk Reference may also provide this information.
• Unwillingness to be transfused with blood components.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Eli Lilly and Company: collaborator
• Incyte Corporation: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

ruxolitinib; abemaciclib

Study Officials

• Raajit Rampal

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raajit Rampal, MD, PhD

CONTACT

646-608-3746; rampalr@mskcc.org

Michael Mauro, MD

CONTACT

646-608-3744

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, non-randomized phase 1 clinical trial evaluating the safety and activity of combined ruxolitinib and abemaciclib in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Patients will be treated in dose escalation using a 3+3 design.

Study Record Dates

• First Submitted: January 26, 2023
• First Posted: February 6, 2023
• Study Start: January 25, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (7)