A Study of Pevonedistat in Adult East Asian Participants

Phase 1

Completed

• Conditions: eukemia, Myeloid, Acute Myelodysplastic Syndromes

• Registration Number: JPRN-jRCT2080223194
• Lead Sponsor: Takeda Pharmaceutical Company Limited

Brief Summary

The recommended clinical dose of pevonedistat in combination with azacitidine in East Asian participants was determined to be pevonedistat 20 mg/m^2 administered on Days 1, 3, and 5 plus azacitidine 75 mg/m^2 on Days 1 through 5, 8, and 9 in a 28-day cycle. -The recommended phase 2/phase 3 dose (RP2/3D) of pevonedistat 20 mg/m^2 in combination with azacitidine 75 mg/m^2 in East Asian participants was the same as determined in Western patient population.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-11
• Results First Posted: 2018-06-16
• Study Completion: 2022-01-25
• Last Update Posted: 17 October 2023

Recruitment & Eligibility

• Status: completed
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

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):
- 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
- 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
- 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
- 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
- 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

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified