Treatment of ITP With Rituximab and / or Accutane

Study Overview
=================
Brief Summary
-----------------
a prospective, multicenter, randomized, open-label, Phase II, two arms interventional trial performed in 5 departments of hematology in China

Detailed Description
-----------------
This is a prospective, multicenter, randomized, open-label, Phase II, two arms interventional trial performed in 5 departments of hematology in China. The investigators explore the efficacy and safety of Rituximab plus short-term methylprednisolone compare standard dose methylprednisolone in newly diagnosed ITP participants.

Official Title
-----------------
Rituximab Plus Short-term Methylprednisolone Versus Standard Dose Methylprednisolone in Newly Diagnosed Participants With Immune Thrombocytopenia (ITP): A Multicenter, Randomized Phase II Study in China

Conditions
-----------------
Immune Thrombocytopenia

Intervention / Treatment
-----------------
* Drug: Rituximab plus methylprednisolone
* Drug: methylprednisolone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Clinically confirmed immune thrombocytopenic purpura (ITP) newly diagnosed Platelet count less than 30×109/L on two occasions or Platelets above 30×109/L combined with bleeding manifestation Subject is ≥ 18 years and ≤80years Subject has signed and dated written informed consent. Fertile patients must use effective contraception during treatment and observational period Negative pregnancy test Exclusion Criteria: Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an aspartate aminotransaminase or alanine aminotransferase level > 3×upper limit of normal Have a New York Heart Classification III or IV heart disease Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures Have active hepatitis B or hepatitis C infection Have a HIV infection Have active infection requiring antibiotic therapy within 7 days prior to study entry Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug Previous treatment with rituximab Previous splenectomy Had previous or concomitant malignant disease Not willing to participate in the study. Expected survival of < 2 years Intolerant to murine antibodies Immunosuppressive treatment within the last month Connective tissue disease Autoimmune hemolytic anemia Patients currently involved in another clinical trial with evaluation of drug treatment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab plus methylprednisolone<br>Combination therapy with rituximab （1000mg IV day1, week 3, week 17 , and week 19）plus short-term methylprednisolone (1mg/kg, oral or IV; reduce to 50% of base dose at week 4, then reduce 8mg every 1 week until stopped). | Drug: Rituximab plus methylprednisolone<br>* rituximab （1000mg IV day1, week 3, week 17 , and week 19）<br>* Other names: monoclone antibody of cluster of differentiation antigen 20;|
| Active Comparator: Methylprednisolone<br>standard dose methylprednisolone alone (1mg/kg, oral or IV; begin to reduce at week 4, reduce 8mg every 2 weeks, then another 8 weeks later reduce 2-4mg every 2-4 weeks). | Drug: methylprednisolone<br>* 1mg/kg, oral or IV; begin to reduce at week 4, reduce 8mg every 2 weeks, then another 8 weeks later reduce 2-4mg every 2-4 weeks<br>* Other names: intravenous methylprednisolone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse free survival | Relapse was defined as a drop in platelet count to <30 ×109/L following an initial best response (partial or complete response). | From date of randomization until the date of relapse or death from any cause, whichever came first, assessed up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative response rate | platelet count ≥ 30 x 10^9/L and at least 2-fold increase of the baseline count, confirmed on at least 2 separate occasions at least 7 days apart, and absence of bleeding. | 1 year | 
| Cumulative complete response rate | platelet count >100 x 10^9/L, confirmed on at least 2 separate occasions at least 7 days apart, and absence of bleeding | 1 year | 
| Cumulative relapse rate | Time to response (from randomization to the achievement of response)Duration of response (from the initial response to the first relapse) | 1 year | 
| adverse event/serious adverse event and cumulative rate of bleeding events | adverse event/serious adverse event associated with study drugs and bleeding events | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune Thrombocytopenia, Rituximab, methylprednisolone