Pevonedistat and Azacitidine in MDS or MDS/MPN Patients Who Fail Primary Therapy With DNA Methyl Transferase Inhibitors
- Conditions
- Myelodysplastic SyndromesMyeloproliferative Neoplasm
- Interventions
- Procedure: Bone Marrow Biopsy & Aspirate
- Registration Number
- NCT03238248
- Lead Sponsor
- Vanderbilt-Ingram Cancer Center
- Brief Summary
This study will evaluate the treatment combination of pevonedistat and azacitidine in the setting of DNA methyltransferase inhibitor(s) failure in patients with relapsed/refractory myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative neoplasm.
- Detailed Description
Primary Objective:
To compare survival of patients treated with a combination of pevonedistat and azacitidine after failure of DNA methyltransferase inhibitors (DNMTi) to historical survival for patients with relapsed/refractory myelodysplastic syndrome (MDS) or myelodysplastic/ myeloproliferative overlap syndromes (MDS/MPN) who are ineligible for hematopoietic stem cell transplant (HSCT)
Secondary Objectives:
* To determine the rate of hematologic improvement (HI) in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure
* To determine the complete remission (CR) and marrow CR rates in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure
* To determine the reduction of bone marrow blasts in patients with relapsed/refractory MDS or MDS/MPN treated with pevonedistat and azacitidine after DNMTi failure
Exploratory Objectives:
* To correlate the mutation burden in patients with relapsed/refractory MDS or MDS/MPN with response to treatment with pevonedistat and azacitidine
* To correlate genomic aberrations with rate of response and survival in relapsed/refractory MDS or MDS/MPN patients treated with pevonedistat and azacitidine
* To measure the effect of pevonedistat treatment in combination with azacitidine on quality of life in patients with relapsed/refractory MDS or MDS/MPN
* To define epigenetic biomarkers for pevonedistat use in relapsed/refractory MDS or MDS/MPN
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 71
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pevonedistat and Azacitidine Azacitidine Subcutaneous Injection or Intravenous Infusion Participants will receive Azacitidine (via an injection under the skin, or via an intravenous infusion (IV bag) on days 1, 2, 3, 4 and 5 of each 28-day cycle. Participants will receive Pevonedistat (through a vein in the arm) on Days 1, 3 and 5 of each 28-day cycle. Pevonedistat and Azacitidine Pevonedistat Infusion Participants will receive Azacitidine (via an injection under the skin, or via an intravenous infusion (IV bag) on days 1, 2, 3, 4 and 5 of each 28-day cycle. Participants will receive Pevonedistat (through a vein in the arm) on Days 1, 3 and 5 of each 28-day cycle. Pevonedistat and Azacitidine Bone Marrow Biopsy & Aspirate Participants will receive Azacitidine (via an injection under the skin, or via an intravenous infusion (IV bag) on days 1, 2, 3, 4 and 5 of each 28-day cycle. Participants will receive Pevonedistat (through a vein in the arm) on Days 1, 3 and 5 of each 28-day cycle.
- Primary Outcome Measures
Name Time Method Overall Survial Time up to 2 years after treatment, a maximum possible duration of 38 months. Overall survival time is defined as time from day 1 in cycle 1 to death for any reason. Patiens alive at last follow up were censored. Overall survival time will be summarized using the method of Kaplan and Meier.
- Secondary Outcome Measures
Name Time Method Time to Progression Up to 24 months, or death Progression-free survival time is defined as time from day1 in cycle 1 to progression or death. Those alive without progression at the last follow up were censored. This survival will be summarized using the method of Kaplan and Meier.
Objective Response Rate Up to 12 months Objective response rate is defined as the percentage of patients with best response of Complete remission (CR), Hematologic improvement (HI), Marrow CR (mCR), or Partial remission (PR) among all patients evaluated. The other categories of response are progressive disease, stable disease and inevaluable. The modified recommendations of the International Working Group (IWG) for Response Criteria for altering natural history of MDS , as well as the International Consortium of clinical experts in MDS/MPN devised uniform response criteria and criteria for disease progression in MDS/MPN overlap syndromes based on three independent academic MDS/MPN workshops (Marsh 2013, December 2013 and June 2014) were used for response assessment.
Rate of Hematologic Response Per IWG Up to 24 months Will assess complete and differential blood counts (peripheral blood), and transfusion requirements. The rate of hematologic improvement is defined as the percentage of patients with only hematologic improvement (defined in the protocol) among all patients evaluated for response.
Trial Locations
- Locations (5)
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
University of Miami Miller School of Medicine
🇺🇸Miami, Florida, United States
Memorial Sloan-Kettering
🇺🇸New York, New York, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States