Trial Title:
A Study of Ruxolitinib in Combination With Abemaciclib for the Treatment of Myelofibrosis
NCT ID:
NCT05714072
Condition:
Myelofibrosis Due to and Following Polycythemia Vera
Conditions: Official terms:
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Conditions: Keywords:
Ruxolitinib
Abemaciclib
22-075
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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.
Primary purpose:
Other
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ruxolitinib
Description:
10mg BID or 15mg BID
Arm group label:
Ruxolitinib plus Abemaciclib
Intervention type:
Drug
Intervention name:
Abemaciclib
Description:
50, 100 and 150 mg
Arm group label:
Ruxolitinib plus Abemaciclib
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- Hemoglobin Patients may receive erythrocyte transfusions to achieve this hemoglobin
level at the discretion of the investigator. Initial treatment must not begin
earlier than the day after the erythrocyte transfusion
- 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.
- Patients who received radiotherapy must have completed and fully recovered from the
acute effects of radiotherapy. A washout period of at least 14 days is required
between end of radiotherapy and randomization
- The effects of ruxolitinib and abemaciclib on the developing human fetus are
unknown. To be eligible for the study, female subjects of childbearing potential
(and their male partners) and men (and female partners) enrolled in the study should
use two methods of effective contraception (hormonal and barrier method of birth
control; abstinence) prior and during the study and also continue to use
contraception for 4 months after completion of ruxolitinib and abemaciclib
administration. Should a woman become pregnant or suspect she is pregnant while she
or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of ruxolitinib and Abemaciclib
administration.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- 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.
- Inability to comprehend or unwilling to sign the informed consent form (ICF).
- Other conditions that, in the opinion of the investigator, may compromise the
achievement of the objectives of the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD,PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Monmouth
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Bergen
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Suffolk - Commack
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampa, MD, PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Westchester
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Phone:
646-608-3746
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Raajit Rampal, MD, PhD
Phone:
646-608-3746
Start date:
January 25, 2023
Completion date:
January 2025
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05714072
http://www.mskcc.org/mskcc/html/44.cfm
