A Study of Pevonedistat in Adult East Asian Participants
Condition: Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Intervention: Pevonedistat 25 mg/m^2; Pevonedistat 44 mg/m^2; Pevonedistat 10 mg/m^2; Pevonedistat 20 mg/m^2; Azacitidine 75 mg/m^2
Intervention description: Pevonedistat 25 mg/m^2 intravenous infusion.; Pevonedistat 44 mg/m^2 intravenous infusion.; Pevonedistat 10 mg/m^2 intravenous infusion.; Pevonedistat 20 mg/m^2 intravenous infusion.; Azacitidine 75 mg/m^2 intravenous or subcutaneous formulation.
Intervention MeSH terms: Azacitidine; Pevonedistat
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the safety and tolerability of pevonedistat
      administered as a single agent and in combination with azacitidine in adult east Asian
      participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).
    

Eligibility criteria:

        Inclusion Criteria include, in part:

          1. East Asian patients aged 18 years or older (or minimum age of legal consent consistent
             with local regulations) when written study informed consent is obtained must meet 1 of
             the following diagnosis criteria for either the Single-Agent Arm or the Combination
             Arm (additional restrictions apply to the Single Agent Arm):

             a. Are male and female participants with WHO-defined AML, including leukemia secondary
             to prior chemotherapy or resulting from an antecedent hematologic disorder, who have
             failed to achieve CR or who have relapsed after prior therapy (R/R) and are not
             candidates for potentially curative treatment, or ii. Are male and female participants
             aged 60 years or older with previously untreated AML who have bone marrow blasts <30%
             and who are not candidates for standard induction chemotherapy, or iii. Are male and
             female participants with WHO-defined MDS that meets the IPSS-R criteria for the very
             high, high, or intermediate risk group, for whom standard curative, life-prolonging
             treatment does not exist or is no longer effective (R/R), or iv. Are male and female
             participants with previously untreated MDS that meets the IPSS-R criteria for the very
             high, high, or intermediate risk group, or vi. Are male and female participants with
             WHO-defined CMML-2 or CMML-1 that meets the IPSS-R criteria for the very high, high,
             or intermediate risk group CMML-1 participants must have bone marrow blasts >=5%

          2. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          3. Able to undergo bone marrow aspiration and biopsy at Screening.

        Exclusion Criteria include, in part:

          1. Acute promyelocytic leukemia (as diagnosed by morphologic examination of bone marrow,
             by fluorescent in situ hybridization or cytogenetics [t (15:17)] of peripheral blood
             or bone marrow, or by other accepted analysis) or AML associated with t (9;22)
             karyotypes or molecular.

          2. More than 3 prior lines of therapy (Combination Arm only).

          3. Prior therapy with hypomethylating agents (example, azacitidine, decitabine).
             (Combination Arm only).

          4. Is eligible for a hematopoietic stem cell transplant.

          5. Is a female participant who is lactating and breastfeeding or who have a positive
             serum pregnancy test during the screening period or a positive urine pregnancy test on
             Day 1 before first dose of study drug.

          6. Had treatment with any investigational products within 14 days before the first dose
             of any study drug.

          7. Has known hypersensitivity to azacitidine or mannitol (Combination Arm only).

          8. Has known central nervous system involvement.

          9. Had systemic antineoplastic therapy or radiotherapy within 14 days before the first
             dose of any study drug, except for hydroxyurea.