Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04281498|
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : May 10, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Accelerated/Blast-phase Myeloproliferative Neoplasm Chronic-phase Myelofibrosis IDH2 Mutation||Drug: Ruxolitinib Drug: Enasidenib||Phase 2|
At this time, there is no standard medical treatment for MPN-AP/BP and most patients with accelerated and blast phase MPN do not respond well to treatment This is a phase II open-label study to evaluate the safety and efficacy of combined ruxolitinib and enasidenib in patients with accelerated/blast-phase myeloproliferative neoplasm or chronic phase myelofibrosis with high risk features and IDH2 mutation.
Ruxolitinib (Jakafi/Jakavi) is FDA approved for myelofibrosis and was shown to reduce splenomegaly and improve symptoms. Enasidenib is a potent inhibitor of the IDH2 mutant enzyme and is FDA approved for relapsed refractory AML where it showed effectivity.
Pre-clinical studies indicate increased disease mitigating effects with the combination of enasidenib and ruxolitinib.
This study will enroll up to 32 patients. Ruxolitinib and enasidenib will be given orally in 28-day cycles.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single Arm open-label Study of Combined Ruxolitinib and Enasidenib in Patients with Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis with an IDH2 Mutation, Simons minimax design.|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Open-label Study of Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation|
|Actual Study Start Date :||January 20, 2021|
|Estimated Primary Completion Date :||May 2024|
|Estimated Study Completion Date :||May 2024|
Experimental: Patients with MPN
Ruxolitinib and Enasidenib combination therapy
Patients who are on ruxolitinib will continue their current dose. Patients who are not on ruxolitinib will receive ruxolitinib dosing based on platelet count
50mg -100mg daily
- Proportion of MPN participants with response [ Time Frame: 6 Months ]The proportion of treated accelerated-phase and blast-phase MPN patients (primary cohort) that achieve a best response of either complete response (CR), Partial Response (PR), or complete response with incomplete recovery of counts (CRi), when treated with the combination of ruxolitinib with enasidenib within 6 cycles of combined therapy.
- Proportion of MPN participants with blast response [ Time Frame: 6 Months ]The proportion of treated accelerated-phase and blast-phase MPN patients that achieve complete (CBR) and partial blast response (PBR).
- Proportion of MF-CP participants with any response [ Time Frame: 6 Months ]The proportion of treated patients with MF-CP and 4%-9% circulating blasts that achieve complete response (CR) Partial Response (PR), clinical improvement (CI) with the combination of ruxolitinib and enasidenib within 6 cycles of combined therapy.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||Yes|
- Subjects must be ≥ 18 years at the time of signing the Informed Consent Form (ICF).
- Understanding and voluntary signing an IRB-approved informed consent form.
- Accelerated-phase (≥ 10% blasts in PB or BM) or blast-phase (≥ 20% blasts in PB or BM) myeloproliferative neoplasm (with history of prior myelofibrosis, polycythemia vera, or essential thrombocythemia)
- Previously treated patients with myelofibrosis with persistent disease or progressive disease (persistent or progressive splenomegaly, leukocytosis, anemia, or thrombocytopenia) with intermediate-1 or greater risk disease according to 2013 International Working Group (IWG) criteria, and 4-9% circulating blasts.
- Demonstration of an IDH2 mutation.
- Platelet count > 75,000 X 109/L for chronic phase myelofibrosis patients.
- Prior therapy with either ruxolitinib or enasidenib is permitted, but not a combination of ruxolitinib and enasidenib.
- Patients with chronic phase myelofibrosis on ruxolitinib must be on the drug for at least 3 months and on a stable dose for at least one month.
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. ECOG 3 status will be allowed if attributable to MPN.
- Patients must have adequate organ function as demonstrated by the following: a. Direct bilirubin < 2.0mg/dL, unless due to Gilbert's disease or current elevations in direct bilirubin associated with existing enasidenib use. b. Serum creatinine< 2.0 mg/dL. c. ALT and AST ≤ 3x upper limit of normal (unless transaminitis is considered to be related to MF).
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to starting enasidenib and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking enasidenib. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- All study participants must be able to swallow oral medication.
- Ability to adhere to the study visit schedule and all protocol requirements.
Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide, G-CSF, lenalidomide, thalidomide clofarabine) except hydroxyurea or experimental drugs, with the exception of ruxolitinib or enasidenib, less than 14 days or 5-half-lives, whichever is longer, prior to starting study therapy and/or lack of recovery from all toxicity (except for alopecia) from previous therapy to Grade 1 or better.
a. Patients will be permitted to receive hydroxyurea while on study for up to a total of 3 cycles of combined therapy.
- Known prior clinically relevant hypersensitivity reaction to ruxolitinib or enasidenib.
- Prior therapy with enasidenib in combination with ruxolitinib.
- Concurrent use of strong inducers of CYP3A4 (Rifampin, St. John's Wort, Carbamazepine, Phenytoin) and/or the following strong inhibitors of CYP3A4 (protease inhibitor containing HIV anti-retrovirals, cobicistat, clarithromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) are prohibited. Also prohibited are CYP2C9 substrate medications that have a narrow therapeutic range: phenytoin and warfarin.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, which places the subject at unacceptable risk if he/she were to participate in the study or which confounds the ability to interpret data from the study.
- Lactating females.
- Active uncontrolled infections.
- Patients with active malignancy of other type than required for this study are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.
- Subject has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke; or left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.
- QTc interval (Fridericia's correction [QTcF]) > 450 ms
All inclusion and exclusion criteria will be reviewed by the Investigator or qualified designee to ensure that the patient qualifies for the trial.
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): NCT04281498
|Contact: Michal Bar-Natan, MDfirstname.lastname@example.org|
|Contact: Raajit Rampal, MD, PhDemail@example.com|
|United States, Arizona|
|Mayo Clinic - Arizona||Not yet recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Jeanne Palmer, MD Palmer.Jeanne@mayo.edu|
|Principal Investigator: Jeanne Palmer, MD|
|United States, California|
|Cedars-Sinai Medical Center||Not yet recruiting|
|Los Angeles, California, United States, 90048|
|Contact: Ronald Paquette, MD 310-423-1160 firstname.lastname@example.org|
|Principal Investigator: Ronald Paquette, MD|
|United States, Florida|
|Moffitt Cancer Center||Not yet recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Andrew T. Kuykendall, MD 813-745-6841 Andrew.Kuykendall@moffitt.org|
|Principal Investigator: Andrew T. Kuykendall, MD|
|United States, Kansas|
|University of Kansas Cancer Center||Not yet recruiting|
|Westwood, Kansas, United States, 66205|
|Contact: Abdulraheem Yacoub, MD 913-588-6029 email@example.com|
|Principal Investigator: Abdulraheem Yacoub, MD|
|United States, Michigan|
|University of Michigan Rogel Cancer Center||Not yet recruiting|
|Ann Arbor, Michigan, United States, 48109-5936|
|Contact: Kristen Pettit, MD 734-764-8195 firstname.lastname@example.org|
|Principal Investigator: Kristen Pettit, MD|
|United States, New York|
|Icahn School of Medicine at Mount Sinai||Recruiting|
|New York, New York, United States, 10029|
|Contact: Lonette Sandy 212-241-4546 Lonette.Sandy@mssm.edu|
|Contact: Amelia Gabler, BS|
|Principal Investigator: Michal Bar-Natan, MD|
|Memorial Sloan-Kettering Cancer Center||Not yet recruiting|
|New York, New York, United States, 10065|
|Contact: Raajit Rampal, MD, PhD 212-639-2194 email@example.com|
|Principal Investigator: Raajit Rampal, MD, PhD|
|United States, North Carolina|
|Wake Forest Baptist Health||Not yet recruiting|
|Winston-Salem, North Carolina, United States, 27157|
|Contact: Rupali Roy Bhave, MD 336-716-1808 firstname.lastname@example.org|
|Principal Investigator: Rupali Roy Bhave, MD|
|United States, Ohio|
|Taussig Cancer Center Institute||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Aaron Gerds, MD, MS 216-445-9840 email@example.com|
|Principal Investigator: Aaron Gerds, MD, MS|
|United States, Texas|
|Mays Cancer Center at UT Health San Antonio||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Ruben Mesa, MD|
|Principal Investigator: Ruben Mesa, MD|
|Princess Margaret Cancer Centre||Not yet recruiting|
|Toronto, Canada, M5G 2M9|
|Contact: Vikas Gupta, MD, FRCP, FRCPath (416) 946-4521 firstname.lastname@example.org|
|Principal Investigator: Vikas Gupta, MD, FRCP, FRCPath|
|Study Chair:||John Mascarenhas, MD||Icahn School of Medicine at Mount Sinai|
|Study Chair:||Ruben Mesa, MD||Mays Cancer Center at UT Health|
|Study Chair:||Ronald Hoffman, MD||Icahn School of Medicine at Mount Sinai|
|Principal Investigator:||Michal Bar-Natan, 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:||
P01CA108671 ( U.S. NIH Grant/Contract )
MPN-RC 119 ( Other Identifier: Myeloproliferative Neoplasms Research Consortium )
|First Posted:||February 24, 2020 Key Record Dates|
|Last Update Posted:||May 10, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Bone Marrow Diseases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Cell Transformation, Neoplastic