Clinical trial NCT04477850: A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions
Official title: A Phase 2, Multicenter, Single-Arm Bridging Study to Evaluate the Efficacy, Pharmacokinetics, and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low or Intermediate Risk Myelodysplastic Syndromes(MDS) in Chinese and Japanese Subjects With Ring Sideroblasts Who Require Red Blood Cell Transfusions
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Keywords: Myelodysplastic Syndromes
MDS
ACE-536
Anemia
Luspatercept
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2020-07-20
Enrollment: 30
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of luspatercept (ACE-536) for the treatment of anemia due to Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) in Chinese and Japanese participants with ring sideroblasts who require Red Blood Cells (RBC) transfusions.


Eligibility criteria: Inclusion Criteria:

* Refractory or intolerant to, or ineligible for, prior Erythropoiesis stimulating agent (ESA) treatment as defined by any one of the following: Refractory to prior ESA treatment, Intolerant to prior ESA treatment, or ESA ineligible.
* previously treated with an ESA or granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, both agents must have been discontinued ≥ 4 weeks prior to date of luspatercept treatment
* Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2

Exclusion Criteria:

* Prior therapy with disease modifying agents for underlying MDS disease
* Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
* Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) or alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN)

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 weeks
timeFrame: Week 1 through Week 24
Secondary outcomes:
measure: RBC-TI ≥ 12 weeks
timeFrame: Week 1 through Week 24
measure: Reduction in Red Blood Cell (RBC) units transfused over 16 weeks compared to baseline
timeFrame: Week 9 through Week 24
measure: Modified hematologic improvement - erythroid (mHI-E) per International Working Group (IWG)
timeFrame: Week 1 through Week 24
measure: Mean hemoglobin increase ≥ 1.0 g/dL
timeFrame: Week 1 through Week 24
measure: Duration of RBC-TI
timeFrame: Week 1 through Week 24
measure: Mean decrease in serum ferritin compared to baseline
timeFrame: Week 9 through Week 24
measure: Mean decrease in iron chelation therapy (ICT) use compared to baseline
timeFrame: Week 9 through Week 24
measure: Time to RBC-TI
timeFrame: Week 1 through Week 24
measure: Progression to acute myeloid leukemia (AML)
timeFrame: Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
measure: Overall survival (OS)
timeFrame: Cycle1 Day1 (each cycle is 21 days) through at least 3 years post first dose
measure: Incidence of type of adverse events (AEs)
timeFrame: Screening through 42 days post last dose
measure: Incidence of frequency of AEs
timeFrame: Screening through 42 days post last dose
measure: Incidence of severity of AEs
timeFrame: Screening through 42 days post last dose
measure: Incidence of seriousness of AEs
timeFrame: Screening through 42 days post last dose
measure: Incidence of relationship of AEs to study treatment
timeFrame: Screening through 42 days post last dose
measure: Pharmacokinetics - Area under the curve (AUC)
timeFrame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
measure: Pharmacokinetics - Maximum plasma concentration of the drug (Cmax)
timeFrame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
measure: Frequency of Anti-drug antibodies (ADA)
timeFrame: Cycle1 Day1 (each cycle is 21 days) through 1-year post first dose
Other outcomes:
Locations:
city: Beijing
country: China
facility: Local Institution - 100
city: Chengdu, Sichuan
country: China
facility: Local Institution - 107
city: Guangzhou
country: China
facility: Local Institution - 105
city: Guangzhou
country: China
facility: Local Institution - 103
city: Guangzhou
country: China
facility: Local Institution - 109
city: Hangzhou City
country: China
facility: Local Institution - 102
city: Nanchang
country: China
facility: Local Institution - 112
city: Nanjing
country: China
facility: Local Institution - 108
city: Shanghai
country: China
facility: Local Institution - 114
city: Shanghai
country: China
facility: Local Institution - 101
city: Suzhu
country: China
facility: Local Institution - 104
city: Tianjin
country: China
facility: Local Institution - 106
city: Wenzhou
country: China
facility: Local Institution - 111
city: Wuhan
country: China
facility: Local Institution - 110
city: Matsuyama
country: Japan
facility: Local Institution - 209
state: Ehime
city: Nagasaki-shi
country: Japan
facility: Local Institution - 203
state: Nagasaki
city: Osakasayama
country: Japan
facility: Local Institution - 210
state: Osaka
city: Kamogawa
country: Japan
facility: Local Institution - 206
city: Mibu-Machi
country: Japan
facility: Local Institution - 201
city: Ogaki
country: Japan
facility: Local Institution - 208
city: Osaka
country: Japan
facility: Local Institution - 205
city: Sagamihara
country: Japan
facility: Local Institution - 204
city: Sendai
country: Japan
facility: Local Institution - 207
city: Shinagawa-ku, Tokyo
country: Japan
facility: Local Institution - 202
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: