Treatment Study for Patients with Higher-Risk MDS, CMML or Low-Blast AML
The purpose of this research study is to evaluate pevonedistat in combination with azacitidine in patients with higher-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or low-blast acute myelogenous leukemia (AML). This study will assess whether receiving pevonedistat in combination with azacitidine increases the amount of time you live without any worsening of your disease when compared to azacitidine alone.
In order to participate you must meet the following criteria:
- Have morphologically confirmed diagnosis of MDS or CMML (i.e., with white blood cell [WBC] <13,000/μL) or low-blast AML.
- For participants with AML (20%-30% blasts): Have a treatment-related mortality (TRM) score >=4 for intensive, induction chemotherapy as calculated using the simplified model described by Walter and coworkers.
Have MDS or CMML and must also have one of the following Prognostic Risk Categories, based on the Revised International Prognostic Scoring System (IPSS-R):
- Very high (>6 points)
- High (>4.5-6 points)
- Intermediate (>3-4.5 points): A participant determined to be in the Intermediate Prognostic Risk Category is only allowable in the setting of >=5% bone marrow myeloblasts.
- Have an Eastern Cooperative Oncology Group (ECOG) status of 0, 1 or 2.
You will be excluded from the study if any of the following criteria apply to you:
- Have had previous treatment for HR MDS or CMML or low-blast AML with chemotherapy or other antineoplastic agents including hypomethylating agent (HMAs) such as decitabine or azacitidine. Previous treatment is permitted with hydroxyurea and with lenalidomide, except that lenalidomide may not be given within 8 weeks before the first dose of study drug.
- Have acute promyelocytic leukemia as diagnosed by morphologic examination of bone marrow, by fluorescent in situ hybridization or cytogenetics of peripheral blood or bone marrow, or by other accepted analysis.
- For participants with AML: Have a WBC count >50,000/ microliter (mcL). Participants who are cytoreduced with leukapheresis or with hydroxyurea may be enrolled if they meet the eligibility criteria.
Are eligible for intensive chemotherapy and/or allogeneic stem cell transplantation. The reason a participant is not eligible for intensive chemotherapy and/or allogeneic stem cell transplantation may consist of one or more of the following factors:
- Are older than 75 years of age.
- Have comorbidities.
- Are not able to tolerate intensive chemotherapy (e.g., participants with AML with 20%-30% blasts and TRM >=4).
- Physician decision (e.g., lack of available stem cell donor).
- The reason a participant is not eligible should be documented in the electronic case report form (eCRF).
This is a partial list of inclusion and exclusion criteria.