A Study of Pevonedistat in Adult East Asian Participants

NCT ID: NCT02782468

Last Updated: 2023-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-16
• Study Completion Date: 2022-01-25

Brief 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).

Detailed Description

The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people with myelodysplastic syndromes MDS (including nonproliferative chronic myelomonocytic leukemia [CMML]) and AML (acute myeloid leukaemia) as a single-agent and in combination treatment with azacitidine. This study will look at the safety and tolerability, the recommended phase 2/phase 3 dose of pevonedistat administered in combination with azacitidine, pharmacokinetics and response to treatment in participants who take single agent pevonedistat compared to participants who take pevonedistat and azacitidine.

The study will enroll approximately 37 participants. Participants will be assigned into one of the four treatment groups which will remain disclosed to the patient and study doctor during the study. Participants will be first enrolled at single-agent low dose level (25 mg/m^2). If this dose is tolerable, participants will be enrolled in parallel at single-agent higher dose level (44 mg/m^2) and in combination treatment cohorts.

• Pevonedistat 25 mg/m^2
• Pevonedistat 44 mg/m^2
• Pevonedistat 10 mg/m^2 and azacitidine 75 mg/m^2 combination
• Pevonedistat 20 mg/m^2 and azacitidine 75 mg/m^2 combination Participants will receive pevonedistat infusion intravenously and azacitidine via intravenous or subcutaneous route.

This multi-center trial will be conducted in Japan, Korea and Taiwan. The overall time to participate in this study is approximately 24 months. Participants will attend the End of Study (EOS) visit for safety, 30 days after receiving their last dose of study drug or before the start of subsequent antineoplastic therapy (other than hydroxyurea).

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1, Cohort 1: Pevonedistat 25 mg/m^2

Pevonedistat, 25 milligram per square meter (mg/m\^2), 60-minute infusion, intravenously, on Days 1, 3 and 5, followed by a rest period of 16 days, in 21-day treatment cycles.

Group Type: EXPERIMENTAL

Pevonedistat 25 mg/m^2

Intervention Type: DRUG

Pevonedistat 25 mg/m\^2 intravenous infusion.

Arm 1, Cohort 2: Pevonedistat 44 mg/m^2

Pevonedistat, 44 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5, followed by a rest period of 16 days, in 21-day treatment cycles.

Group Type: EXPERIMENTAL

Pevonedistat 44 mg/m^2

Intervention Type: DRUG

Pevonedistat 44 mg/m\^2 intravenous infusion.

Arm 2, Cohort 1: Pevonedistat 10 mg/m^2+ Azacitidine 75 mg/m^2

Pevonedistat 10 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m\^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.

Group Type: EXPERIMENTAL

Pevonedistat 10 mg/m^2

Intervention Type: DRUG

Pevonedistat 10 mg/m\^2 intravenous infusion.

Azacitidine 75 mg/m^2

Intervention Type: DRUG

Azacitidine 75 mg/m\^2 intravenous or subcutaneous formulation.

Arm 2, Cohort 2: Pevonedistat 20 mg/m^2+ Azacitidine 75 mg/m^2

Pevonedistat 20 mg/m\^2, 60-minute infusion, intravenously, on Days 1, 3, and 5 and azacitidine 75 mg/m\^2, on Days 1 to 5, and Days 8 and 9, intravenously or subcutaneously, followed by a rest period of 19 days, in 28-day treatment cycles.

Group Type: EXPERIMENTAL

Pevonedistat 20 mg/m^2

Intervention Type: DRUG

Pevonedistat 20 mg/m\^2 intravenous infusion.

Azacitidine 75 mg/m^2

Intervention Type: DRUG

Azacitidine 75 mg/m\^2 intravenous or subcutaneous formulation.

Interventions

Pevonedistat 25 mg/m^2

Pevonedistat 25 mg/m\^2 intravenous infusion.

Intervention Type: DRUG

Pevonedistat 44 mg/m^2

Pevonedistat 44 mg/m\^2 intravenous infusion.

Intervention Type: DRUG

Pevonedistat 10 mg/m^2

Pevonedistat 10 mg/m\^2 intravenous infusion.

Intervention Type: DRUG

Pevonedistat 20 mg/m^2

Pevonedistat 20 mg/m\^2 intravenous infusion.

Intervention Type: DRUG

Azacitidine 75 mg/m^2

Azacitidine 75 mg/m\^2 intravenous or subcutaneous formulation.

Intervention Type: DRUG

Eligibility Criteria

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):

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Maebashi, , Japan

Nagoya, , Japan

Sendai, , Japan

Tokyo, , Japan

Chonnam National University Hwasun Hospital

Jeonnam, , South Korea

Severance Hospital Yonsei University Health System - PPDS

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Countries

Japan; South Korea; Taiwan

References

Handa H, Cheong JW, Onishi Y, Iida H, Kobayashi Y, Kim HJ, Chiou TJ, Izutsu K, Tsukurov O, Zhou X, Faessel H, Yuan Y, Sedarati F, Faller DV, Kimura A, Wu SJ. Pevonedistat in East Asian patients with acute myeloid leukemia or myelodysplastic syndromes: a phase 1/1b study to evaluate safety, pharmacokinetics and activity as a single agent and in combination with azacitidine. J Hematol Oncol. 2022 May 11;15(1):56. doi: 10.1186/s13045-022-01264-w.

Reference Type: DERIVED

PMID: 35545778 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1166-8630

Identifier Type: OTHER

Identifier Source: secondary_id

Pevonedistat-1012

Identifier Type: -

Identifier Source: org_study_id