Study of Combination Ruxolitinib and Decitabine Treatment for Accelerated Phase MPN or Post-MPN AML
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|ClinicalTrials.gov Identifier: NCT02076191|
Recruitment Status : Completed
First Posted : March 3, 2014
Last Update Posted : February 28, 2019
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|Condition or disease||Intervention/treatment||Phase|
|Myeloproliferative Neoplasms||Drug: Ruxolitinib Drug: Decitabine||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||49 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Phase I/II Trial of Ruxolitinib in Combination With Decitabine in Patients With Accelerated Phase Myeloproliferative Neoplasm (MPN) or Post-MPN AML|
|Study Start Date :||February 2014|
|Actual Primary Completion Date :||July 20, 2018|
|Actual Study Completion Date :||July 20, 2018|
Experimental: Myeloproliferative neoplasms
In phase I, increasing doses of ruxolitinib in combination with decitabine at a dose of 20 mg/m2 daily intravenously over 5 days. An initial dose of ruxolitinib of 10 mg orally twice daily is anticipated with planned, dose escalations of 15 mg orally twice daily, 25 mg orally twice daily and 50 mg orally twice daily. The dose can also be de-escalated to 5mg orally twice daily if dose limiting toxicities (DLTs) are observed at the initial 10mg dose. Patients will receive ruxolitinib as a single agent for the first 7 days followed by the administration of decitabine on day 8 for a total of 5 consecutive days. Patients will continue ruxolitinib at the assigned dose through the first cycle and may reduce the dose for specified toxicity beginning with the second cycle. Patients in Phase II will start at the recommended phase II dose (RPTD) of ruxolitinib in combination with decitabine at a dose of 20 mg/m2 daily intravenously over 5 days.
Ruxolitinib will be administered at doses of 5mg, 10mg, 15mg, or 25 mg taken orally every 12 hours throughout the treatment cycle.
Decitabine is administered intravenously at a dose of 20 mg/m2 daily for 5 days. Subsequent cycles of decitabine may be administered at 4 week intervals as clinically tolerated. Decitabine treatment may be deferred for up to 2 weeks to allow recovery from non-hematologic toxicity during the first 6 cycles and up to 2 weeks thereafter for hematologic toxicities as well. The first treatment cycle will last 35 days and will be the evaluable period for DLTs and RPTD determination for patients enrolled in the phase I portion only. Subsequent treatment cycles will be 4-6 weeks in duration as defined by decitabine administration.
- Maximum Tolerated Dose (MTD) [ Time Frame: up to 5 weeks ]Safety and efficacy of ruxolitinib when used in combination with decitabine. MTD is defined as the highest dose studied for which the incidence of (Dose Limiting Toxicities) DLT is at least 33%.
- Dose Limiting Toxicities (DLT) [ Time Frame: up to 5 weeks ]Safety and efficacy of ruxolitinib when used in combination with decitabine. DLTs will be defined as those adverse events occurring in the first 5 weeks after initiation of therapy that are not clearly related to disease.
- Recommended Phase II Dose (RPTD) [ Time Frame: up to 20 weeks ]Safety and tolerability of drug combination of ruxolitinib and decitabine. RPTD is that dose level below the MTD for which the incidence of DLT is <33%.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Accelerated phase MPN as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of acute myelogenous leukemia as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF.
- >18 years of age
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to accelerated or blastic phase MPN and not due to another comorbidity.
- Acceptable pre-study organ function during screening as defined as: Total bilirubin < 1.5 times the upper limit of normal (ULN) unless due to Gilbert's disease or hemolysis, Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN, Serum creatinine ≤ 1.5 x ULN
- Women of childbearing potential and males must agree to use adequate contraception (i.e., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a female subject become pregnant or suspect she is pregnant while participating in this study, she should inform the treating physician immediately.
- Patients who are not candidates for or have declined an allograft.
- Ability to understand and willingness to sign a written informed consent document.
- Have had chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry. Previous treatment with either ruxolitinib or decitabine as single agents will not exclude eligibility. Previous stem cell transplant will also not exclude eligibility as long as other inclusion/exclusion criteria have been met.
- Patients with acute myelofibrosis are excluded.
- Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Other medications, severe acute/chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, that in the judgment of the Investigator would make the subject inappropriate for entry into this study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02076191
|United States, Missouri|
|Washington University of St. Louis|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Wake Forest University Baptist Medical Center|
|Winston-Salem, North Carolina, United States, 27157|
|United States, Ohio|
|Cleveland Clinic Taussig Cancer Center Institute|
|Cleveland, Ohio, United States, 44195|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Study Chair:||John Mascarenhas, MD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||Ronald Hoffman, MD||Icahn School of Medicine at Mount Sinai|
|Responsible Party:||John Mascarenhas, Associate Professor, Icahn School of Medicine at Mount Sinai|
|Other Study ID Numbers:||
MPD-RC 109 ( Other Identifier: Myeloproliferative Disorders-Research Consortium )
P01CA108671 ( U.S. NIH Grant/Contract )
|First Posted:||March 3, 2014 Key Record Dates|
|Last Update Posted:||February 28, 2019|
|Last Verified:||February 2019|
Bone Marrow Diseases
Molecular Mechanisms of Pharmacological Action