Efficacy and Safety of Ultra Small Dose Decitabine for the Lower Risk MDS Patients With Transfusion Dependent

A Single-center Prospective Clinical Trial of the Efficacy and Safety of Ultra Small Dose Decitabine for the Lower Risk Myelodysplastic Syndrome Patients With Transfusion Dependent

Myelodysplastic syndrome (MDS) is widely recognized as a clonal hematopoietic stem cell disorder. Decitabine has been approved for the treatment of all subtypes of myelodysplastic syndrome (MDS). However, the use of decitabine is often limited by its severe toxicity represented by myelosuppression even at relatively low doses. In lower-risk patients (including IPSS low and int-1 risk groups), treatment mainly aims at improving cytopenias, especially anemia. However, although several drugs may improve anemia, sometimes durably, most of lower risk MDS eventually require red blood cell (RBC) transfusions during their disease course. Long term RBC transfusions lead to iron overload mainly due to an increase in reticulo-endothelial iron recycling.Cardiac, liver and endocrine (diabetes mellitus) dysfunction due to iron overload and often leading to fatal outcome has been reported in heavily transfused lower risk MDS patients.

To date, the optimal regimen for decitabine treatment is not well established. In this study, we perform a prospective analysis to explore the decitabine schedule for the treatment of lower risk myelodysplastic syndrome patients with transfusion dependent.

Study Overview

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

Detailed Description

The investigators are undertaking a single-center, single-arm study of 50 lower risk myelodysplastic syndrome patients with transfusion dependent from Shandong University Qilu Hospital . All the participants are selected to receive ultra small dose decitabine treatment (given intravenously at a dose of 3.5mg/m2, qd x 5d, every four weeks for one cycle). A routine blood examination is performed twice every week. Bone marrow (BM) is examined with routine aspirate smear and G-banding analysis every 1-2 treatment courses to evaluate responses.Adverse events are also recorded throughout the study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Qilu Hospital, Shandong University
      • Principal Investigator: Ming Hou
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Shandong University Qilu Hospital
      • Contact: Ming Lv
      • Principal Investigator: Ming Hou, Dr

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:

• diagnosis of MDS
• The IPSS [17] score ≤ 1
• patients with transfusion dependent
• Adequate hepatic and renal function (aspartate aminotransferase [AST] ≤ 2.5 x upper normal limit, alanine aminotransferase [ALT] ≤ 2.5 x upper normal limit, bilirubin ≤ 1.5 x upper normal limit and creatinine < 2 x upper normal limit, Ccr > 60ml/min ).

Exclusion Criteria:

• Decitabine and Arsenic trioxide allergy
• Pregnancy and lactation
• Cardiovascular disease
• ECOG score > 2
• HCV, HIV, HBsAg seropositive status

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultra small dose decitabine; Decitabine 3.5mg/m2，ivdrip，qd x 5d, every four weeks for one cycle. It will be given six cycles.	Drug: decitabine; Decitabine 3.5mg/m2，ivdrip，qd x 5d, every four weeks for one cycle. It will be given six cycles.; Other Names: ultra small dose decitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete response	Bone marrow blasts not more than 5%, absolute neutrophil count more than 1*10^9/L, HgB more than 100g/L, and platelet count more than 100*10^9/L.	30 days from the emrollment

Collaborators and Investigators

• Sponsor: Shandong University
• Investigators: Principal Investigator: Ming Lv, Doctor, Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Anticipated): December 30, 2018
• Study Completion (Anticipated): July 30, 2020

Study Registration Dates

• First Submitted: February 3, 2017
• First Submitted That Met QC Criteria: February 6, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: February 6, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Decitabine Myelodysplastic syndrome
• 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: lower risk MDS-decitabine

Plan for Individual participant data (IPD)

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