Clinical Trials/NCT01566695

NCT01566695

Completed

Phase 3

A Phase 3, Multicenter, Randomized, Double-blind Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo Plus Best Supportive Care in Subjects With Red Blood Cell Transfusion-dependent Anemia and Thrombocytopenia Due to IPSS Lower-risk Myelodysplastic Syndromes.

Celgene196 sites in 2 countries216 target enrollmentApril 26, 2013

ConditionsMyelodysplastic Syndrome

InterventionsOral Azacitidine Best Supportiv Care (BSC)Placebo

DrugsOral Azacitidine Placebo

Overview

Phase: Phase 3
Intervention: Oral Azacitidine
Conditions: Myelodysplastic Syndrome
Sponsor: Celgene
Enrollment: 216
Locations: 196
Primary Endpoint: Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).

Registry

clinicaltrials.gov

Start Date

April 26, 2013

End Date

December 21, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Celgene

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18 years or older
•Have a documented diagnosis of MDS
•Anemia that requires red blood cell transfusions
•Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization
•Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
•Must agree to follow pregnancy precautions as required by protocol.
•Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted

Exclusion Criteria

•Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
•Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is \>= 8 weeks prior to inclusion into the study).
•Prior allogeneic or autologous stem cell transplant
•Eligible for allogenic or autologous stem cell transplant
•History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect
•Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
•Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization
•Ongoing medically significant adverse events from previous treatment, regardless of the time period
•Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS)
•Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system is allowed)

Arms & Interventions

Oral Azacitidine

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Intervention: Oral Azacitidine

Oral Azacitidine

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Intervention: Best Supportiv Care (BSC)

Placebo

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Intervention: Placebo

Placebo

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Intervention: Best Supportiv Care (BSC)

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days

Time Frame: Each participant was assessed for at least 56 days or more; from the date of randomization of study drug up to the data cut-off date of 25 January 2019, approximately 5 months.

RBC transfusion (tfx) independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 56 days (i.e., day 1 to day 56, day 2 to day 57) were considered as a 56-day RBC transfusion independent responder.

Secondary Outcomes

Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days(From the date of randomization of study drug up to the data cut-off date of 25 January 2019)
Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days(From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants Who Achieved RBC Transfusion Independence for ≥ 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days)(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Time to Platelet Transfusion Independence(From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Overall Survival (OS)(From randomization up to death from any cause; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS(Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo)
Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)(From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group)
Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML(From randomization of study drug to progression of AML; up to a maximum of approximately 10 years on study; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Percentage of Participants With Significant Bleeding Events(From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo)
Number of Participants With Treatment Emergent Adverse Events (TEAE)(From first dose of IP up to 28 days after the last dose of IP or until the last study visit; up to a maximum of approximately 6 months on study)
Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6(Baseline to Cycle 6 Day 1)
Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6(Baseline to Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6(Cycle 6 Day 1)
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 2 Day 1 (C2D1)(From Baseline to Cycle 2 Day 1 (C2D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 3 Day 1 (C3D1)(From Baseline to Cycle 3 Day 1 (C3D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 4 Day 1 (C4D1)(From Baseline to Cycle 4 Day 1 (C4D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 5 Day 1 (C5D1)(From Baseline to Cycle 5 Day 1 (C5D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 6 Day 1 (C6 D1)(From Baseline to Cycle 6 Day 1 (C6 D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - Cycle 7 Day 1 (C7D1)(From Baseline to Cycle 7 Day 1 (C7D1))
Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5 - End of Treatment(From Baseline to End of Treatment)
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6(From Baseline to Cycle 6 Day 1)
Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)
Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years(From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo)