CLINICAL TRIAL / NCT06291987
Ivosidenib and Ruxolitinib in Patients With Advanced Myeloproliferative Neoplasms (MPNs) That Have an IDH1 Gene Mutation
- Interventional
- Recruiting
- NCT06291987
Contact Information
A Phase 1b Trial of Ivosidenib Combined With Ruxolitinib in IDH1-Mutated Advanced-Phase MPNs
The purpose of this research is to gather information on the safety and effectiveness determining maximum tolerated dose (MTD) of ruxolitinib in combination with ivosidenib in IDH1-mutated advanced-phase Ph-negative MPNs while evaluate the efficacy of ruxolitinib in combination with ivosidenib in IDH1-mutated advanced-phase Ph-negative MPNs.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
Accepts Healthy Volunteers
Inclusion Criteria:
- Advanced-Phase IDH1-mutated Ph-negative MPNs (both untreated and
relapsed/refractory) including any of the following:
- polycythemia vera with (PV) ≥ 5% peripheral or bone marrow blasts at time of
screening
- essential thrombocythemia (ET) with ≥ 5% peripheral or bone marrow blasts at
time of screening
- primary myelofibrosis (PMF) with ≥ 5% peripheral or bone marrow blasts at time
of screening
- Atypical CML with ≥ 5% peripheral or bone marrow blasts at time of screening
- MPN-NOS with ≥ 5% peripheral or bone marrow blasts at time of screening
- MDS/MPN Overlap Syndromes including CMML with ≥ 5% peripheral or bone marrow
blasts at time of screening
- post-PV myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time
of screening
- post-ET myelofibrosis with ≥ 5% blasts peripheral or bone marrow blasts at time
of screening
- primary and secondary myelofibrosis with inadequate response to JAK inhibitor
regardless of blast percentage. Inadequate response to JAK inhibitor will be
defined as lack of achieving any clinical improvement criteria within 12 weeks
of of JAK inhibitor initiation.
- Patients can be on cytoreduction at time of study enrollment with hydroxyurea or
steroids.
- Age ≥18 years.
- ECOG performance status ≤2
- Patients must have normal organ and marrow function as defined below:
- Creatinine clearance ≥60 mL/min, determined by the Cockroft-Gault formula, OR
serum creatinine ≤ 1.5 x ULN
- AST and ALT ≤3 x ULN and bilirubin ≤1.5 x ULN (unless considered due to
Gilbert's syndrome, leukemic involvement, or extravascular hemolysis in the
spleen)
- A platelet count of 50 x 109/L should be met for those with chronic-phase
myelofibrosis and < 5% blasts peripherally or in bone marrow
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial.
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated. Patients with
a history of hepatitis C virus (HCV) infection must have been treated and cured. For
patients with HCV infection who are currently on treatment, they are eligible if
they have an undetectable HCV viral load.
- Other eligibility criteria include the following:
- Patients must be at least 4 weeks from major surgery, radiation therapy, or
participation in other investigational trials, and must have recovered from
clinically significant toxicities related to these prior treatments.
- The effects of the investigational agents on the developing human fetus are
unknown. For this reason, women of child-bearing potential and men must agree
to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Patients cannot be on concomitant chemotherapy, radiation therapy, or immunotherapy
other than as specified in this protocol. Patients cannot have had prior treatment
with ivosidenib.
- Patients with a "currently active" second malignancy other than non-melanoma skin
cancers. Patients are not considered to have a "currently active" malignancy if they
have completed therapy and are free of disease or they are not currently requiring
treatment for an indolent malignancy. Patients with APL and active CNS disease would
also be excluded
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to ivosidenib or ruxolitinib.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, venous thromboembolism, stroke, active chronic liver disease (eg chronic
alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary
biliary cholangitis, hemochromatosis) or psychiatric illness/social situations that
would limit compliance with study requirements.
- Subject has QTc interval ≥ 450 msec or other factors that increase the risk of QT
prolongation or arrhythmic events at screening unless due to bundle branch block or
pacemaker with approval of the principal investigator.
- Pregnant women are excluded from this study because ruxolitinib and ivosidenib carry
the potential for teratogenic or abortifacient effects. Because there is an unknown
but potential risk for adverse events in nursing infants secondary to treatment of
the mother with ruxolitinib and ivosidenib, breastfeeding should be discontinued if
the mother is treated with any of these agents.
- Patient is known to have dysphagia, short-gut syndrome, gastroparesis, or other
conditions that limit the ingestion or gastrointestinal absorption of drugs
administered orally.
- Patients receiving any medications or substances that are inhibitors or inducers of
CYP3A4 should have eligibility and alternative medications reviewed by site PI.