Completed

A Survival Study in Patients With High Risk Myelodysplastic Syndromes Comparing Azacitidine Versus Conventional Care

0 criteria met from your profileSee at a glance how your profile meets each eligibility criteria.
What is being tested

Azacitidine

+ Physician Choice
Drug
Other
Who is being recruted

Myelodysplastic Syndromes

Over 18 Years
+20 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Other Study

Phase 3
Interventional
Study Start: November 2003

See protocol details

Summary

Principal SponsorCelgene
Last updated: October 29, 2019
Sourced from a government-validated database.Claim as a partner
Study start date: November 1, 2003Actual date on which the first participant was enrolled.

The purpose of this study is to determine whether patients with high-risk myelodysplastic syndromes (MDS) treated with azacitidine have improved survival compared to conventional care treatments. The study will also assess the effect of treatments on response, duration of response, and transformation to acute myeloid leukemia (AML). The study will continue for 12 months following last patient enrolled. See study AZA PH GL 2003 CL 001 E for information about the extension to this study. Comparison/Control Interventions offered the physician three options: * Best supportive care (BSC) alone, * Low-dose cytarabine subcutaneously for 14 days every 28 to 42 days, or * Standard chemotherapy administered for induction as a continuous intravenous infusion of cytarabine over 7 days plus an anthracycline (daunorubicin, idarubicin, or mitoxantrone) on Days 1, 2, and 3; and, for those eligible, 1 or 2 consolidation cycles administered as continuous intravenous infusions of cytarabine for 3 to 7 days with the same anthracycline that was used at induction on Days 1 and 2 (each cycle between 28 to 70 days from the start of the previous cycle). All three options included best supportive care. Neither the experimental group (azacitidine) nor any of the comparison/control options allowed use of erythropoietin. Duration of Intervention: Patients will be treated until death, withdrawal, unacceptable toxicity or conclusion of the study.

Official TitleA Multicenter, Randomized, Open-label, Parallel-group, Phase 3 Trial of Subcutaneous Azacitidine Plus Best Supportive Care Versus Conventional Care Regimens Plus Best Supportive Care for the Treatment of Myelodysplastic Syndromes (MDS) 
Principal SponsorCelgene
Last updated: October 29, 2019
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
358 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Other Study
Some studies explore topics that don't fall into a specific category. These might include innovative research, new technologies, or emerging healthcare areas.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Myelodysplastic Syndromes
Criteria
7 inclusion criteria required to participate
Have a diagnosis of refractory anemia with excess blasts or refractory anemia with excess blasts in transformation according to the French-American-British classification system for myelodysplastic syndromes (MDS) and a relatively high risk of acute myeloid leukemia (AML) transformation, with an International Prognostic Scoring System score of INT-2 or High
Be 18 years of age or older
Have a life expectancy of at least 3 months
Be unlikely to proceed to bone marrow or stem cell transplantation therapy following remission

Show More Criteria

13 exclusion criteria prevent from participating
Secondary myelodysplastic syndromes (MDS)
Prior treatment with azacitidine
Prior history of acute myeloid leukemia (AML)
Malignant disease diagnosed within prior 12 months

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Study Drug plus best supportive care. Treatment with erythropoietin was not permitted
Group II
Active Comparator
Physician choice of low dose cytarabine (plus best supportive care), standard chemotherapy (plus best supportive care) or best supportive care (only). Treatment with erythropoietin was not permitted
Study Objectives
Primary Objectives

Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact.

Kaplan-Meier estimates for the median months until death from any cause within the intent-to-treat population. Patients surviving at the end of the follow-up period were censored at the date of last contact. If a patient withdrew consent to follow-up or was lost to follow-up, the patient was censored as of the last date of contact. Subgroups that were analyzed are age, gender, French-American-British (FAB) classification, World Health Organization (WHO) classification and International Prognostic Scoring System (IPSS) classification.

Count of participants who died during the study
Secondary Objectives

The time to transformation to AML or death from any cause (whichever occurred first) was defined as the number of days from the date of randomization until the date of documented AML transformation or death from any cause. Patients who did not transform to AML or die were censored at the date of last follow-up.

The time to transformation to AML was defined as the number of days from the date of randomization until the date of documented AML transformation, defined as a bone marrow blast count ≥ 30% independent of baseline bone marrow count. Patients who did not transform to AML were censored at the date of last follow-up or date of death.

Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from red blood cell (RBC) transfusion at baseline and during treatment, for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were dependent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Summary of dependence and independence from platelet transfusion at baseline and during treatment for patients who were independent at baseline. A patient was considered transfusion independent at baseline if the patient had no transfusions during the 56 days prior to randomization. During study, a patient was considered transfusion independent during the on-treatment period if the patient had no transfusions during any 56 consecutive days or more. Otherwise, the patient was considered transfusion dependent.

Investigator determined responses followed IWG criteria for * complete remission(CR): repeat bone marrow show \<5% myeloblasts, and peripheral blood evaluations lasting \>=2 months of hemoglobin(\>110 g/L), neutrophils(\>=1.5x10\^9/L), platelets(\>=100x10\^9/L), blasts (0%) and no dysplasia * partial remission(PR) is the same as CR for peripheral blood: bone marrow shows blasts decrease by \>=50% or a less advanced FAB classification from pretreatment * stable disease(SD) is a failure to achieve at least a partial remission, but with no evidence of progression for at least 2 months.

IWG 2000 Criteria: Pretreatment=hemoglobin \<100g/L or RBC transfusion-dependent, platelet count \<100x10\^9/L or platelet transfusion dependent, absolute neutrophil count \<1.5x10\^9/L. Erythroid response: Major-\>20g/L increase or transfusion independent. Minor- 10-20g/L increase or \>=50% decrease in transfusion requirements. Platelet response: Major-absolute increase of \>=30x10\^9/L or platelet transfusion independence. Minor-\>=50% increase. Neutrophil response: Major-\>=100% increase or an absolute increase of \>0.5x10\^9/L. Minor-\>=100% increase and absolute increase of \<0.5x10\^9/L.

The time to disease progression, relapse after complete or partial remission (CR, PR), or death from any cause was defined as the time from the date of randomization until the first date of documented disease progression, relapse after CR or PR, or death from any cause.

The duration of improvement was defined as the time from the date of hematologic improvement until the date of first documented progression or relapse after hematologic improvement or death from any cause.

The on-treatment adverse event rate of infection requiring IV antibiotics, antifungals, or antivirals per patient-years. The on-treatment period was considered the period from the date of randomization to the last treatment study visit.

Patient counts for a variety of subsets of adverse experiences for the core study period (day 1 to 42 months). The individual options for Conventional Care Regimens (Best Supportive Care Only, Low-Dose Cytarabine, and Standard Chemotherapy) are presented as separate treatments.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 108 locations
Suspended
University of Alabama School of MedicineBirmingham, United StatesSee the location
Suspended
Indiana University Cancer CenterIndianapolis, United States
Suspended
Washington University School of MedicineSaint Louis, United States
Suspended
Mount Sinai Medical CenterNew York, United States
Completed108 Study Centers