Clinical trial NCT01599325: Study of Azacitidine to Evaluate Safety and Effectiveness for Chinese Patients With Higher Risk Myelodysplastic Syndrome
Official title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneous Azacitidine in Adult Chinese Subjects With Higher-Risk Myelodysplastic Syndromes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome (MDS)
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-05-16
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

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;
  * 10% 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;
* Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted;
* Able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

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;
* Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study;
* Any condition that confounds the ability to interpret data from the study.

Primary outcomes:
measure: 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.
timeFrame: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
measure: Percentage of Participants With a Hematologic Response Using IWG Criteria for MDS and Assessed by the Investigator
timeFrame: Response initially assessed at end of cycle 6, then every 4 cycles; Up to 29 January 2015; 894 days
measure: 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.
timeFrame: Up to 29 January 2015; 894 days
Secondary outcomes:
measure: The Number of Units of Platelet Transfusions by Cycle
timeFrame: 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
measure: The Number of Platelet Transfusions by Cycle
timeFrame: 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
measure: The Number of Units of Red Blood Cell (RBC) Transfusions by Cycle
timeFrame: 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
measure: The Number of RBC Transfusions by Cycle
timeFrame: 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
measure: The Number of Infections (Post-baseline Average) Requiring Intravenous (IV) Antibiotics, Anti-fungals, or Antivirals by Cycle
timeFrame: 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
measure: Kaplan Meier Estimates for Overall Survival (OS)
timeFrame: Until the end of the survival follow-up period; Up to data cut-off of 29 January 2015; 894 days
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Parent Phase
timeFrame: Up to 29 January 2015; from the first dose of study drug to 28 days after the date of the last dose of study drug (maximum time on study was 244 days)
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Maximum Observed Plasma Concentration (Cmax) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Time to Maximum Plasma Concentration (Tmax) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Terminal Phase of Half-life (T1/2) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Apparent Total Plasma Clearance (CL/F) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Apparent Volume of Distribution (Vd/F) of Azacitidine
timeFrame: PK blood samples collected at 0.25, 0.5, 1,2,3,4, 6 and 8 hours after azacitidine administration on Day 7
measure: Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Extension Phase
timeFrame: Up to final data cut off date of 25 April 2018; from the first dose of study drug extesnion of 29 December 2014 to 28 days after the date of the last dose of study drug; median duration of any dose of study drug was 169 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: The 301 Hospital- Chinese PLA General Hospital
city: Beijing
country: China
facility: The Third Hospital of Peking University
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Hangzhou
country: China
facility: 1st Hospital Zhejiang University (The First Affiliated Hospital of Zhejiang University )
city: Shanghai
country: China
facility: Ruijin Hospital Shanghai Jiaotong University
city: Shanghai
country: China
facility: Shanghai 6th Hospital
city: Suzhou
country: China
facility: The 1st Hospital of Soochow University
city: Tianjin
country: China
facility: Blood Disease Hospital, Chinese Academy of Medical Science and Peking Union Medical College
city: Wuhan
country: China
facility: Wuhan Union Hospital
Study officials:
affiliation: Celgene
name: C L Beach
role: STUDY_DIRECTOR
References: