Clinical trial NCT01719692: Low-dose Rituximab Regimens in Chinese Adult Patients With Immune Thrombocytopenia
Official title: Prospective Multi-center Randomized Controlled Low-dose Rituximab Regimens in Chinese Adult Patients With Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Immune Thrombocytopenic Purpura
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Langfang Traditional Chinese Medicine Hospital
name: Henan Cancer Hospital
name: The Second Affiliated Hospital of Kunming Medical University
First posted: 2012-11-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A comparative study with rituximab (100 mg weekly for 4 weeks and 375mg/m2 for once) shows low dose rituximab may be a useful alternative therapy in patients with ITP.The aim of this study is to compare the efficacy and tolerability of two different regimens of low doses rituximab for the treatment of adult patients with ITP.

Detailed description: This is a multicentre, prospective, open-label, randomised controlled trial. The aim of this study will compare the long-term efficacy and safety of two low-dose rituximab regimens in adult Chinese patients with glucocorticoid-resistant/dependent or relapsed ITP. Group A will receive rituximab100 mg weekly for four weeks, and group B will receive rituximab 375 mg/m2 once. After initiating treatment, if the patient has at least two consecutive evaluations (interval \>7 days) without rescue therapy and a platelet count \>50×109/L, the concomitant medications such as glucocorticoids can be reduced or stopped.

Within 3 months of the last rituximab dose, rescue therapy is recommended if the patient has an extremely low platelet count and an obvious bleeding tendency. Rescue therapy is limited to IVIG (0.4 g/kg per day for 3-5 days) and glucocorticoid (methylprednisolone 0.8 mg/kg per day for 7-14 days or equivalent dose of other glucocorticoids).

Eligibility criteria: Inclusion Criteria:

* Age 18-60 years old;
* Diagnosis of primary immune thrombocytopenia according to the guidelines of American Society of Hematology for at least 3 months before inclusion;
* Platelet count \<30×109/L (measured at least twice during the screening, with at least a 1-week interval);
* Failed or dependent on or relapsed after previous treatment with glucocorticoid;
* If on glucocorticoid maintenance therapy, dose ≤0.5 mg/kg prednisone or equivalent and stabilised for at least 4 weeks;
* Drugs such as azathioprine, danazol, cyclosporine A, tacrolimus, and sirolimus stopped for at least 4 weeks;
* Splenectomy more than 6 months previously;
* Previous rescue therapy of ITP (including methylprednisolone, platelet transfusion and IVIG) completed at least 2 weeks before the first administration;
* Liver and kidney function (including alanine aminotransferase, aspartate aminotransferase, total bilirubin, serum creatine, urea nitrogen, etc.) less than 1.5 times the upper limit of normal value;
* Eastern Cooperative Oncology Group performance status ≤2;
* Cardiac function classification (New York Heart Association) ≤2;
* Understand the research procedure and voluntarily sign a written informed consent form.

Exclusion Criteria:

* Patients with secondary thrombocytopenia (including myelodysplastic syndrome, aplastic anemia, common variant immunodeficiency disease, hereditary thrombocytopenia, drug-induced thrombocytopenia, pseudothrombocytopenia, connective tissue disease secondary thrombocytopenia, thrombocytopenia after liver disease, etc.);
* Previous treatment of RTX or allergic to RTX;
* Uncontrollable primary diseases of important organs (including malignant tumor, liver failure, heart failure, kidney failure and other diseases);
* HIV-positive status;
* Active infection including hepatitis B (HBV), hepatitis C (HCV) and other viral antigens or DNA, RNA positive; cytomegalovirus, Epstein-Barr virus, syphilis chronic or active infection. If HBV core antibodies are positive, HBV-DNA testing is required.
* Extensive and severe bleeding, such as hemoptysis, upper gastrointestinal hemorrhage, intracranial hemorrhage, etc.
* Heart disease or arrhythmia need treatment, or poorly controlled hypertension;
* Thrombotic diseases including pulmonary embolism, thrombosis, atherosclerosis, etc.;
* Previously allogeneic stem cell transplantation or organ transplantation;
* Mental disorders who are unable to obtain informed consent normally and participate in trials and follow-up;
* Symptoms of toxicity from pre-trial treatment have not resolved;
* Other severe conditions that may limit participation in the trial (e.g., diabetes; severe cardiac insufficiency; myocardial infarction or unstable arrhythmia or unstable angina within the last 6 months; gastric ulcer; active autoimmune diseases, etc.);
* Sepsis or other irregular bleeding;
* Taking antiplatelet drugs;
* pregnancy, suspected pregnancy (urine human chorionic gonadotropin positive during screening) or lactation.

Primary outcomes:
measure: Overall response rate at week 12
timeFrame: Patients will be followed for 6 months at least after Rituximab treatment.
Secondary outcomes:
measure: Sustained response rate over 6 months and 1, 2, 3, 4, and 5 years after RTX initiation
timeFrame: Patients will be followed for 6 months at least after Rituximab treatment.
measure: Time to response (TTR)
timeFrame: 6 months
measure: Number of subjects with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale
timeFrame: 3 months
measure: Adverse events assessment
timeFrame: 12 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Hospital of Blood disease
state: Tianjin
Study officials:
affiliation: Hospital of Blood disease
name: RENCHI YANG, Dr
role: PRINCIPAL_INVESTIGATOR
References: