A Phase 2/3, Multicenter, Randomized, Dose Optimization (Part I), Double-blind (Part II) Study to Compare the Efficacy and Safety of Oral Azacitidine (Oral-Aza, ONUREG®) plus Best Supportive Care (BSC) versus Placebo plus BSC in Participants with IPSS-R Low- or Intermediate-risk Myelodysplastic Syndrome (MDS)

Celgene Corp.52 sites in 10 countries166 target enrollmentMarch 10, 2023

Overview

Phase: Phase 2/3
Intervention: Not specified
Conditions: Not specified
Sponsor: Celgene Corp.
Enrollment: 166
Locations: 52
Primary Endpoint: For Part I (Phase 2) - AEs evaluated using NCI CTCAE criteria, v.5.0, including TEAEs, laboratory assessments, and vital signs
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

For Part I (Phase 2) The primary objective is to evaluate the safety and efficacy (CR within 6 cycles) of 2 Oral-Aza dose regimens, and to recommend the optimal dose for the Phase 3 study (RP3D) based on the totality of safety, efficacy, PK, and PD data. For Part II (Phase 3) The primary objective is to evaluate the CR (as defined in the statistical consideration section) within 6 cycles for both study arms

Registry

euclinicaltrials.eu

Start Date

March 10, 2023

End Date

TBD

Last Updated

last year

Investigators

Sponsor

Celgene Corp.

Responsible Party

Principal Investigator

GSM-CT

Scientific

Celgene Corp.

Eligibility Criteria

Inclusion Criteria

•Male and female participants must be ≥ 18 years of age at the time of signing the informed consent.
•Participant has a documented diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of low- or intermediate-risk disease (low IPSS-R score: > 1.5 and ≤ 3.0; intermediate IPSS-R score: > 3.0 and ≤ 4.5). For participants in South Korea, the IPSS-R score for inclusion in Part II (Phase 3) is > 1.5 and ≤ 3.
•MDS subtypes may include (MDS with single lineage dysplasia [MDS-SLD], MDS with multilineage dysplasia [MDS-MLD], MDS with ring sideroblasts [MDS-RS] [SLD or MLD], MDS unclassifiable [MDS-U], MDS with excess blasts-1 [MDS-EB1], MDS with deletion of 5q [MDS-del(5q)], therapy related myeloid neoplasm [t-MN]). MDS diagnosis, WHO classification, and IPSS-R risk classification will be prospectively determined by independent central pathology and cytogenetics review, and applicable central laboratory results
•Participant has at least 1 cytopenia (anemia, thrombocytopenia, or neutropenia) meeting one of the protocol defined criteria.
•Have an Eastern Cooperative Oncology Group ECOG performance status of 0, 1, or 2.

Exclusion Criteria

•Participants with prior malignancies must have 1) an expected median life expectancy of at least 12 months at the time of inclusion and 2) no active treatment of any sort for at least 24 weeks prior to randomization (including but not limited to immunotherapy or targeted therapy).
•Hypoplastic MDS with a marrow cellularity of ≤ 10%
•Participants diagnosed with MDS-EB2
•Overlap syndrome (MDS/MPN), CMML, atypical chronic myeloid leukemia (CML), unclassifiable myeloproliferative disorder (MPD), and MDS with moderate to extensive marrow fibrosis (Grade 2 or 3).
•Significant active cardiac disease within the previous 6 months.
•Known history of Human Immunodeficiency Virus (HIV) or Hepatitis C Virus (HCV) infection, or evidence of active Hepatitis B Virus (HBV)
•Participants with an absolute neutrophil count (ANC) of less than 0.5 × 109/L within a week (7 days) of randomization or other laboratory abnormalities as defined in Section 6.
•Prior treatment with azacitidine (any formulation), decitabine, or other hypomethylating agent.
•Prior treatment with lenalidomide unless the participant received the last dose ≥ 8 weeks prior to randomization.
•Use of excluded treatment within 35 days prior to randomization as defined in Section 6.2

Outcomes

Primary Outcomes

For Part I (Phase 2) - AEs evaluated using NCI CTCAE criteria, v.5.0, including TEAEs, laboratory assessments, and vital signs

For Part I (Phase 2) - Achievement of CR per IWG 2006 criteria within 6 cycles

For Part II (Phase 3) - Achievement of CR within 6 cycles

Secondary Outcomes

For Part I (Phase 2) - Achievement of OR within 6 cycles (CR, PR, mCR, HI-E, HI-P, H-IN per IWG 2006 criteria), best OR; OR duration
For Part I (Phase 2) - CR duration
For Part I (Phase 2) - Achievement of 84-day pRBC-TI within 6 cycles; pRBC-TI duration
For Part I (Phase 2) - Achievement of 84-day PLT-TI within 6 cycles; PLT-TI duration
For Part II (Phase 3) - Achievement of 84-day pRBC-TI within 6 cycles
For Part II (Phase 3) - pRBC-TI duration
For Part II (Phase 3) - Achievement of 84-day platelet-TI within 6 cycles
For Part II (Phase 3) - Platelet-TI duration
For Part II (Phase 3) - Achievement of pRBC transfusion reduction; pRBC transfusion reduction duration
For Part II (Phase 3) - CR duration
For Part II (Phase 3) - Achievement of OR within 6 cycles (CR, PR, mCR, HI-E, HI-P, H-IN per IWG 2006 criteria), best OR; OR duration
For Part II (Phase 3) - OS, EFS (event: death, AML, MDS-EB 2), time to AML, time to subsequent therapy
For Part II (Phase 3) - Iron parameters
For Part II (Phase 3) - AEs evaluated using NCI CTCAE criteria, v.5.0, including TEAEs, laboratory assessments and vital signs
For Part II (Phase 3) - Change from baseline in the FACT-An, QUALMS, and EQ-5D-5L
For Part II (Phase 3) - Evaluation of healthcare resource use (eg, hospitalization) associated with IP during study