Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation
- Conditions
- Accelerated/Blast-phase Myeloproliferative NeoplasmChronic-phase MyelofibrosisIDH2 Mutation
- Interventions
- Registration Number
- NCT04281498
- Lead Sponsor
- John Mascarenhas
- Brief Summary
The presence of IDH mutation is associated with worse survival in patients with myelofibrosis. Moreover IDH mutations are among the most frequently encountered events in MPNs that have progressed to acute myeloid leukemia. Ruxolitinib, a JAK1/2 inhibitor, and enasidenib an IDH2 inhibitor are effective and tolerable treatments for patients with myelofibrosis (MF) and acute myeloid leukemia (AML), respectively. The study team hypothesize that the combination of these agents in patients with MPN with an IDH2 mutation will improve the overall clinical response to therapy.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Patients with MPN Ruxolitinib Ruxolitinib and Enasidenib combination therapy Patients with MPN Enasidenib Ruxolitinib and Enasidenib combination therapy
- Primary Outcome Measures
Name Time Method Number of MPN Participants With Response 6 Months The number of treated accelerated-phase and blast-phase MPN patients (primary cohort) that achieve a best response per 2013 International Working Group (IWG) criteria 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.
Complete Response with incomplete recovery of counts (CRi) - complete remission (\<5% marrow blasts by morphology) with incomplete count recovery (platelet count \<100 x 10\^9\^/L and/or absolute neutrophil count \< 1 x 10\^9\^/L)
Complete Response (CR) - full marrow recovery; full count recovery; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Partial Response (PR) - morphologic remission in the peripheral blood but not necessarily in the bone marrow; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
- Secondary Outcome Measures
Name Time Method Number of MPN Participants With Blast Response 6 Months The number of treated accelerated-phase and blast-phase MPN patients that achieve complete (CBR) and partial blast response (PBR).
Number of MF-CP Participants With Any Response 6 Months The number 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.
Trial Locations
- Locations (11)
Taussig Cancer Center Institute
🇺🇸Cleveland, Ohio, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Mays Cancer Center at UT Health San Antonio
🇺🇸San Antonio, Texas, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Mayo Clinic - Arizona
🇺🇸Scottsdale, Arizona, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
University of Michigan Rogel Cancer Center
🇺🇸Ann Arbor, Michigan, United States