Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome

NCT01599325 | Completed Phase 2 Results

• 1 other identifier: AZA-MDS-002
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of the study is to determine whether azacitidine is safe and effective in the treatment of Chinese patients with higher risk Myelodysplastic Syndromes (MDS).

Conditions

Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With a Hematologic Response Based on the International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Programmatically Assessed by the Sponsor Using Clinically Relevant Data.

  Hematologic Response is defined by those participants who experienced a Complete Response, Partial Response and Stable Disease (SD) based on IWG 2000 response criteria for MDS. CR = repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia • PR = same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment • Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months. • Failure: death during treatment or disease progression • Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence • Disease Progression: change in blast levels • Disease Transformation to Acute Myelogenous Leukemia.

  Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days

• Percentage of Participants With a Hematologic Response Using IWG Criteria for MDS and Assessed by the Investigator

  Hematologic Response is defined by those participants who experienced a Complete Response, Partial Response and Stable Disease (SD) based on IWG 2000 response criteria for MDS. CR = repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia • PR = same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment • Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months. • Failure: death during treatment or disease progression • Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence • Disease Progression: change in blast levels • Disease Transformation to Acute Myelogenous Leukemia.

  Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days

• Percentage of Participants Achieving a Hematologic Improvement (HI) Based on 2000 IWG Response Criteria for MDS and Programmatically Assessed by the Sponsor Using Clinically Relevant Data.

  Hematologic improvements (HI) have 4 categories: 1. Erythroid response (HI-E): Major \>20g/L increase or transfusion independent. Minor: 10-20g/L increase or ≥50% decrease in transfusion requirements. 2. Platelet response (HI-P): Major absolute increase of ≥30x10\^9/L or platelet transfusion independence. Minor: ≥50% increase. 3. Neutrophil response (HI-N): Major 100% increase or an absolute increase of \>0.5x10\^9/L. Minor: ≥100% increase and absolute increase of \<0.5x10\^9/L 4. Progression or relapse after HI Hematological improvement (HI) was defined as any type (major or minor) of improvement of HI-E, HI-P, or HI-N. 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. Sponsor's determination was derived using clinically relevant data. Denominator for progression/relapse after HI included participants who had achieved HI.

  Up to 29 January 2015; 894 days

Secondary Outcomes (15)

• The Number of Units of Platelet Transfusions by Cycle

  Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days

• The Number of Platelet Transfusions by Cycle

  Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days

• The Number of Units of Red Blood Cell (RBC) Transfusions by Cycle

  Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days

• The Number of RBC Transfusions by Cycle

  Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days

• The Number of Infections (Post-baseline Average) Requiring Intravenous (IV) Antibiotics, Anti-fungals, or Antivirals by Cycle

  Up to cycle 27; The on-treatment period was considered the period from the date of first dose to the last treatment study visit; Up to 29 January 2015; 894 days

Study Arms (1)

Azacitidine

EXPERIMENTAL

Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days until disease progression (DP), adverse events (AE), withdrawal of consent from further treatment, withdrawal of consent, death, lost to follow-up, or protocol violation.

Drug: Azacitidine

Interventions

Azacitidine DRUG

Subcutaneous administration of azacitidine 75 mg/m\^2/day for 7 days every 28 days optimally for at least 6 cycles until disease progression, unacceptable toxicity, or treatment discontinuation for any other reason

Also known as: Vidaza

Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Chinese males and females of Asian descent ≥ 18 years of age at the time of signing the informed consent document;
• Must have a documented diagnosis of refractory anemia with excess blasts (RAEB) or refractory anemia with excess blasts in transformation (RAEB-T) according to French-American-British (FAB) classification for Myelodysplastic Syndrome (MDS) and with an International Prognostic Scoring System (IPSS) score of intermediate-2 or high risk or a diagnosis of myelodysplastic chronic myelomonocytic leukemia (CMML) per modified FAB criteria meeting the following:
• Monocytosis in peripheral blood \> 1 x 10\^9/L;
• Dysplasia in one or more myeloid cell lines;
• % to 29% blasts in the bone marrow; and White blood cell (WBC) count \< 13 x 10\^9/L
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 ;
• Adequate organ function, defined as:
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN);
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.0 times the ULN;
• Serum Creatinine ≤ 1.5 times the ULN;
• Females of childbearing potential (FCBP) must:
• Agree to the use of a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on azacitidine; and
• for 3 months following the last dose of azacitidine; and have a negative serum pregnancy test within 72 hours prior to starting Investigational Product (IP).
• Male subjects with a female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and avoid fathering a child during the course of the study and for 3 months following the last dose of azacitidine;

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Previous treatment with azacitidine or decitabine;
• Diagnosis of malignant disease within the previous 12 months (excluding basal cell carcinoma of the skin without complications, "in-situ" carcinoma of the cervix or breast, or other local malignancy excised or irradiated with a high probability of cure);
• Uncorrected red cell folate deficiency or vitamin B12 deficiency;
• Diagnosis of metastatic disease;
• Malignant hepatic tumors;
• Known or suspected hypersensitivity to azacitidine or mannitol;
• Candidate to proceed to bone marrow or stem cell transplant during the study;
• Prior transplantation or cytotoxic therapy, including azacitidine and chemotherapy, administered to treat MDS;
• Treatment with erythropoietin or myeloid growth factors (granulocyte colony-stimulating factor \[G-CSF\] or granulocyte-macrophage colony-stimulating factor \[GM-CSF\]) during the 21 days prior to Day 1 of Cycle 1;
• Treatment with androgenic hormones during the 14 days prior to Day 1 of Cycle 1;
• Active viral infection with known human immunodeficiency virus (HIV) or viral hepatitis type B or C;
• Treatment with other investigational drugs, including thalidomide and arsenic trioxide, within the previous 30 days prior to Day 1 of Cycle 1, or ongoing adverse events from previous treatment with investigational drugs, regardless of the time period; and
• Pregnant or lactating females;
• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study;

Sponsors & Collaborators

• Celgene: lead

Study Sites (11)

Peking University People's Hospital

Beijing, 100044, China

Location

The 301 Hospital- Chinese PLA General Hospital

Beijing, 300200, China

Location

The Third Hospital of Peking University

Beijing, China

Location

West China Hospital of Sichuan University

Chengdu, 610041, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

1st Hospital Zhejiang University (The First Affiliated Hospital of Zhejiang University )

Hangzhou, 310003, China

Location

Ruijin Hospital Shanghai Jiaotong University

Shanghai, 200025, China

Location

Shanghai 6th Hospital

Shanghai, 200233, China

Location

The 1st Hospital of Soochow University

Suzhou, 215006, China

Location

Blood Disease Hospital, Chinese Academy of Medical Science and Peking Union Medical College

Tianjin, 300041, China

Location

Wuhan Union Hospital

Wuhan, 430000, China

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

1-888-260-1599

Study Officials

• C L Beach

  Celgene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: May 16, 2012
• Study Start: July 24, 2012
• Primary Completion: January 29, 2015
• Study Completion: March 13, 2018
• Last Updated: March 19, 2019
• Results First Posted: February 29, 2016

Record last verified: 2019-03

Locations

CN (11)