A Clinical Trial Evaluating the Efficacy of Ultra Low Dose of Decitabine in Myelodysplastic Syndromes (MDS)

Prospective, Open, Multi-center, Double Arm Clinical Trial Evaluating the Efficacy of Ultra Low Dose of Decitabine in Myelodysplastic Syndromes (MDS)

To evaluate the safety and clinical efficacy of ultra-low-dose decitabine in Chinese MDS

Study Overview

• Status: Unknown
• Conditions: Myelodysplastic Syndromes (MDS)
• Intervention / Treatment: Drug: decitabine

Detailed Description

To develop a highly effective and safe protocol, a multi-center, prospective clinical trial was conducted in China, with aims to evaluate the grade III and IV hematologic toxicity and clinical efficacy of subcutaneous injection of ultra-low-dose decitabine (5 to 7 mg/m2) for treatment of myelodysplastic syndrome (MDS), while decitabine at a dose of 20 mg/m2 as a control.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guangsheng He, MD.PhD; Phone Number: 008615312052789; Email: heguangsheng@medmail.com.cn

Study Locations

• China
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Not yet recruiting
      • No.303 Hospital of Chinese People's Liberation Army
      • Contact: Xiaolin Yin; Email: 13321717899@163.com
      • Principal Investigator: Xiaolin Yin
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
      • Contact: Guangsheng He
      • Principal Investigator: Guangsheng He
      • Sub-Investigator: Jianping Mao
  • Liaoning
    • Shenyang, Liaoning, China, 110022
      • Recruiting
      • Shengjing Hospital of China Medical Univercity
      • Principal Investigator: Wei Yang
      • Contact: Wei Yang; Email: yangw@sj-hospital.org
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
      • Contact: Mei Zhang; Email: zhangmei@medmail.com.cn
      • Principal Investigator: Mei Zhang
  • Xinjiang
    • Urumqi, Xinjiang, China, 830001
      • Not yet recruiting
      • People's Hospital of Xinjiang Uygur Autonomous Region
      • Contact: Xiaomin Wang; Email: wxm201304@163.com
      • Principal Investigator: Xiaomin Wang
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Not yet recruiting
      • Zhejiang Provincial Hospital of TCM
      • Contact: Jianping Shen; Email: ouyangguifang@medmail.com.cn
      • Principal Investigator: Jianping Shen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men or women aged 18 to 80 years;
2. Patients at high risk of MDS assessed by International Prostate Symptom Score (IPSS);
3. Chronic myelomonocytic leukemia (CMML) patients with abnormal white blood cell counts, extremely low platelet count or organ infiltration (such as hepatomegaly, splenomegaly) that required therapy;
4. Patients at low risk of MDS identified by IPSS score who had secondary MDS, platelet count of < 20*10^9/L, no response to erythropoietin (EPO) (non-5q deletion syndrome) in the presence of disease symptoms or blood transfusion dependence, or no response to EPO/lenalidomide (5q deletion syndrome) in the presence of disease symptoms or blood transfusion dependence;
5. Patients with a Eastern Cooperative Oncology Group (ECOG) of 0 to 2;
6. Patients with an expected lifespan of over 6 months;
7. Patients with a aspartate aminotransferase (AST) of < 2.5 times higher than the normal upper limit, alanine aminotransferase (ALT) of < 2.5 times higher than the normal upper limit, total bilirubin of < 1.5 times higher than the normal upper limit, and serum creatinine of < 1.5 times higher than the normal upper limit;
8. Subjects who had recovery of toxicity, did not undergo any therapy 4 weeks prior to the first trial, and did not receive nitrosourea therapy and bone marrow transplantation 6 weeks prior to the first trial;
9. Female subjects were menopausal, underwent surgical sterilization, or had effective contraception (oral contraceptive, injectable contraceptive, intrauterine device, contraceptive patch, male sterilization) prior to enrollment and during the trial, and were negative for serum or urine pregnancy test at screening;
10. No insemination was given to male subjects during the treatment and within 2 months post-treatment;
11. Subjects complying with the study protocol;
12. Subjects that signed the informed consent, which indicated they understood the purpose, the procedure and potential benefits of the trial and were willing to participate in the trial.

Exclusion Criteria:

1. Patients that were diagnosed as acute myeloid leukemia (primitive bone marrow cell proportion of 20% or higher) or other progressive malignant diseases;
2. Patients that received treatment with other drugs within 30 days prior to the first administration of decitabine;
3. Patients that received radiotherapy within 14 days prior to the first administration of decitabine;
4. Patients with uncontrolled heart disease or congestive heart failure;
5. Patients with uncontrolled restrictive or obstructive pulmonary disease;
6. Patients with active viral, bacterial or invasive fungal infections;
7. Patients that were complicated by autoimmune hemolytic anemia or immune thrombocytopenia;
8. Patients with a history of use of azacitidine or decitabine;
9. Patients that were sero-positive for HIV;
10. Patients with mental or other disorders that cannot completely cooperate with the treatment or follow up;
11. Patients bone marrow cannot be sampled;
12. Subjects that were allergic to decitabine vehicle;
13. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultra-low-dose group; decitabine was subcutaneously administered at 5 to 7 mg/m2 once daily for successive 3 days at the first week, and once daily at weeks 2 to 4, with a total dose of 60 mg in a 4-week cycle.	Drug: decitabine
Active Comparator: Low-dose group; decitabine was subcutaneously given at 20 mg/m2 once daily for successive 3 days, with a total dose of 60 mg/m2 in a 4-week cycle.	Drug: decitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Grade III and IV hematologic toxicity, according to National Cancer Institute common toxicity criteria (NCI-CTC) V3.0 criteria	8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response, according to International Working Group (IWG) response criteria		8 months
Complete response (CR) rate of bone marrow, according to IWG response criteria		8 months
Partial response (PR) rate, according to IWG response criteria		8 months
Hematologic improvement (HI), according to IWG response criteria		8 months
Overall response rate, defined as CR＋PR＋HI, according to IWG response criteria		8 months
Cytogenetic response, according to IWG response criteria		8 months
times of transfusion requirements	times of transfusion requirements during 8 months after enrollment	8 months
times of hospitalization	times of hospitalization during 8 months after enrollment	8 months
The quality of life, the quality of life will be assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30)		8 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University
• Investigators: Principal Investigator: Guangsheng He, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimate): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): November 8, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: MDS-ULD-2016; ChiCTR-IPR-16008100 (Other Grant/Funding Number: Chinese Clinical Trial Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED