Myelodysplastic Syndrome--CDA-2 Hematological Improvement National Affirmation Study

Study Overview
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Brief Summary
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This Study aims to evaluate the efficacy and safety of CDA-2 in the treatment of International Prognostic Scoring System (IPSS) Lower/Intermediate-risk myelodysplastic syndrome (MDS) in Chinese patients.

Detailed Description
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Patients with lower/intermediate-risk myelodysplastic syndrome (MDS) have rare therapeutic options other than supportive care. In pilot studies, CDA-2 showed promising results of hematological improvement in these patients. To date, the optimal regimen for CDA-2 treatment is not well established. The researchers are going to make a multi-centered clinical trial to evaluate the efficacy and safety of CDA-2 in 800 patients with International Prognostic Scoring System(IPSS) Lower/Intermediate-risk myelodysplastic syndrome (MDS). Eligible patients will be given CDA-2 intravenously, with 200 ml each day for 14 consecutive days in every four weeks (one cycle). The treatment will be repeated at least for 3 cycles. The patients will be followed up to 24 weeks. The primary endpoint is hematological improvement (HI) at 12 weeks according to IWG criteria. Full blood counts will be done on all patients every week. Change in bone marrow function as measured by changes in bone marrow morphology and cytogenetics will be assessed before and after 3 cycles of the treatment. The secondary endpoint is the therapy response. Complete remission (CR), partial remission (PR) and response duration, side effects, evaluation of QOL will be evaluated at the end of the treatment in every cycle. Adverse events of the treatment will be recorded for evaluation of the safety.

Official Title
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The Efficacy and Safety of CDA-2 for the Treatment of IPSS Lower/Intermediate-risk Myelodysplastic Syndrome Patients: a Multi-centered Prospective Open Study

Conditions
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Myelodysplastic Syndrome (MDS)

Intervention / Treatment
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* Drug: CDA-2 (Cell Differentiation Agent 2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets IPSS-R classification of low, or intermediate-1 risk disease. Subject is 18 to 85years of age the time of signing the informed consent form (ICF). Able to adhere to the study visit schedule and other protocol requirements Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. Laboratory test results within these ranges: Serum creatinine </=1.5 mg/dL x Upper limit of the normal (ULN),Blood urine nitrogen (BUN)</=1.5 mg/dL x Upper limit of the normal (ULN),Total bilirubin </=1.5 mg/dL x Upper limit of the normal (ULN),Serum glutamic oxaloacetic transaminase/aspartate transaminase (SGOT/AST) and Serum glutamic pyruvic transaminase/alanine transaminase (SGPT/ALT)</=2 x Upper limit of the normal (ULN). No prior intensive combination chemotherapy or dose Azacitidine,Decitabine,and Lenalidomide,etc. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent. Exclusion Criteria: IPSS risk group intermediate-2 or high risk breast feeding and pregnant women MDS associated with del 5q cytogenetic abnormality Patients with history of hepatitis B, C, HIV(+), alcoholic liver disease or evidence of hepatopathy will be excluded. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDA-2 (Cell Differentiation Agent 2)<br>Patients will be given CDA-2 therapy. | Drug: CDA-2 (Cell Differentiation Agent 2)<br>* CDA-2 will be given intravenously, with 200 ml each day for 14 consecutive days in every four weeks (one cycle). The treatment will be repeated at least for 3 cycles.<br>* Other names: Uroacitides (a compound mixed of peptides and organic acids);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological Improvement (HI) at 12 Weeks | Hematologic improvement (HI) per International Working Group (IWG),HI: hemoglobin increase of >= 1.5 g/dL, platelet increase of >= 30,000/mL (starting with > 20,000/mL), neutrophils increase of >= 100% and > 500/μL. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate of The Therapy at 12 Weeks | IWG 2006 response criteria - CR: bone marrow evaluation shows <= 5% blasts; normal maturation of all cells lines (mCR), peripheral blood evaluation shows hemoglobin >= 11 g/dL, neutrophils >= 1000/mL, platelets >= 100,000/mL, 0% blasts; PR: Same as CR, except blasts decrease >= 50%, still greater than 5% in bone marrow | 12 weeks | 
| Red Blood Cell Transfusion Independence (RBC-TI) in 24 weeks | Proportion of subjects who are Red blood cell (RBC) transfusion free over any consecutive 84-day period within 24 weeks | 24 weeks | 
| Change From Baseline to that of the 24 weeks of Scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ C-30) Physical Functioning Scale | The EORTC QLQ will be evaluated for each patients at the beginning and end of the study. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDA-2, MDS