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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pemphigus
• Intervention / Treatment: Drug: Rituximab and Cyclophosphamide IV

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • PGIMER
  • Chandigarh, India, 160012
    • Post-graduate Institute of Medical Education and Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rituximab; Inj Rituximab 1 gram IV given on day 0 and day 15	Drug: Rituximab and Cyclophosphamide IV
Active Comparator: Combination of Rituximab and Cyclophosphamide IV; 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
To study the difference in relapse rate	upto 9 months
to study the total cumulative dose of corticosteroids adminstered and adjuvants required among patients of the 2 treatment groups	upto 9 months

Collaborators and Investigators

• Sponsor: Uprety Shraddha
• Collaborators: Postgraduate Institute of Medical Education and Research
• Investigators: Principal Investigator: Shraddha Uprety, MBBS, Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Anticipated): June 1, 2015
• Study Completion (Anticipated): June 1, 2015

Study Registration Dates

• First Submitted: October 4, 2013
• First Submitted That Met QC Criteria: October 27, 2013
• First Posted (Estimate): November 1, 2013

Study Record Updates

• Last Update Posted (Estimate): October 30, 2014
• Last Update Submitted That Met QC Criteria: October 29, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Rituximab; Pemphigus; Rituximab and IV cyclophosphamide combination; B cell re-population characteristics following Rituximab
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigus; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Rituximab
• Other Study ID Numbers: 9187-PG-2012