Comparative Study of Rituximab Versus Combination of Rituximab and Intravenous Cyclophosphamide in Severe Pemphigus

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness of rituximab alone vs combination of rituximab and cyclophosphamide in the treatment of pemphigus not responding adequately to routine medications.

Official Title
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A PILOT STUDY TO ASSESS THE EFFICACY OF RITUXIMAB VERSUS COMBINATION OF RITUXIMAB AND INTRAVENOUS CYCLOPHOSPHAMIDE IN THE TREATMENT OF REFRACTORY PEMPHIGUS

Conditions
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Pemphigus

Intervention / Treatment
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* Drug: Rituximab and Cyclophosphamide IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with the diagnosis of pemphigus based on clinical, histopathological and immunological features the following: Refractory disease defined as continuing extension of old lesions, development of new lesion, or failure of established lesions to begin to heal despite 3 weeks of therapy on 1.5 mg/kg/day of prednisolone or its equivalent with or without the concurrent use of cyclophosphamide 2mg/kg/day for 12 weeks or azathioprine 2.5 mg/kg/day for 12 weeks. Patients who fail to respond to 6 DCP/DP are also considered as refractory disease. Exclusion Criteria: Infections- Hepatitis B, Hepatitis C, HIV, active tuberculosis or sepsis. Abnormal liver function tests and renal function tests Known cardiac arrhythmia or conduction abnormality Systolic ejection fraction <40% Pregnancy and breast feeding Severely decreased bone marrow functions. Known history of bladder cancer or hemorrhagic cystitis Known allergy to cyclophosphamide Patients of reproductive age group who haven't completed their family Known hypersensitivity to murine proteins. Patients who do not consent for the study.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rituximab<br>Inj Rituximab 1 gram IV given on day 0 and day 15 | Drug: Rituximab and Cyclophosphamide IV<br> <br> |
| Active Comparator: Combination of Rituximab and Cyclophosphamide IV<br>IV Rituximab 1gram on day 0 and 15 750 mg IV cyclophosphamide in 250 ml of NS over 2-3 hr on day 1 and day 16 | Drug: Rituximab and Cyclophosphamide IV<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study the clinical efficacy of IV rituximab vs IV rituximab and IV cyclophosphamide combination for treatment of refractory pemphigus in terms of early and late end points as defined by the international pemphigus committee | Primary outcome measures being Time taken for control of disease activity Time taken for achievement of partial remission Time taken for achievement of complete remission | upto 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study the characteristics of B cell depletion and repopulation following IV rituximab and combination of IV cyclophosphamide with IV rituximab. | Flowcytometric analysis of CD19+ve27-ve naïve B cells count, CD19+ve27+ve memory B cells count and CD24highCD38high transitional cell count will be performed at baseline, 3rd month, 6th month and 9th month. | upto 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pemphigus, Rituximab, Rituximab and IV cyclophosphamide combination, B cell re-population characteristics following Rituximab