FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2024/03/064428 [Registered on: 19/03/2024] Trial Registered Prospectively
Last Modified On: 01/03/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Single Arm Study 
Public Title of Study   Bortezomib-dexamethasone combination for the treatment of patients with warm autoimmune hemolytic anemia 
Scientific Title of Study   Weekly bortezomib-dexamethasone as a third-line therapy for patients with warm autoimmune hemolytic anemia 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ankur Jain 
Designation  Assistant Professor, Clinical Haematology 
Affiliation  Vardhman Mahavir Medical College and Safdarjung Hospital 
Address  Department of Haematology, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi-110029

South West
DELHI
110029
India 
Phone  9910265555  
Fax    
Email  drankur589@yahoo.in  
 
Details of Contact Person
Scientific Query  
Name  Dr Ankur Jain 
Designation  Assistant Professor, Clinical Haematology 
Affiliation  Vardhman Mahavir Medical College and Safdarjung Hospital 
Address  Department of Haematology, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi-110029


DELHI
110029
India 
Phone  9910265555  
Fax    
Email  drankur589@yahoo.in  
 
Details of Contact Person
Public Query  
Name  Dr Ankur Jain 
Designation  Assistant Professor, Clinical Haematology 
Affiliation  Vardhman Mahavir Medical College and Safdarjung Hospital 
Address  Department of Haematology, Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi-110029


DELHI
110029
India 
Phone  9910265555  
Fax    
Email  drankur589@yahoo.in  
 
Source of Monetary or Material Support  
Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi-110029 
 
Primary Sponsor  
Name  Safdarjung Hospital 
Address  Vardhman Mahavir Medical College and Safdarjung Hospital, Delhi-110029 
Type of Sponsor  Government medical college 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ankur Jain  Safdarjung Hospital  Department of Haematology, Old Sports Injury Complex building, Safdarjung Hospital, New Delhi-110029
South West
DELHI 		 9910265555

drankur589@yahoo.in 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
vardhman Mahavir Medical College and Safdarjung Hospital  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D591||Other autoimmune hemolytic anemias,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Bortezomib-dexamethasone  Bortezomib-dexamethasone will be administered once every week in patients with warm autoimmune hemolytic anaemia (wAIHA) who fail both prednisolone and rituximab. patients will be treated with bortezomib (1.3 mg per m2 subcutaneously per week) and dexamethasone (40 mg per oral per week, Vd). Acyclovir (400 mg twice a day) will be used as prophylaxis for herpes zoster reactivation during treatment and until 3 months following bortezomib discontinuation. Initially, weekly assessments will be done with complete blood count, corrected reticulocyte count, serum lactate dehydrogenase (LDH), and liver function tests till partial response (PR), after which, the frequency of testing will be reduced to monthly intervals, or earlier, in case of clinical suspicion of relapse (worsening dyspnea, fatigue). Treatment with weekly Vd will be given till complete response (CR). In case, no CR is achieved after 1 year, treatment with weekly Vd will be continued till the partial response (PR). Once sustained complete response (CR) or partial response (in case of PR at 1 year) is achieved with weekly Vd, treatment will be gradually tapered in an attempt to achieve treatment free remission (TFR). During tapering, Vd will be administered once every two weeks (2 weekly Vd). For patients relapsing on 2 weekly Vd, treatment will be changed to Vd lite [bortezomib (1.3 mg per m2 subcutaneous per week) and dexamethasone (20 mg per week oral). Treatment will be discontinued once sustained CR is achieved with either 2 weekly Vd, or Vd lite. Patients will be followed up for a minimum of two year. Responses will be recorded as PR, CR, sustained CR, and no response (NR) and duration of response (DOR), and bortezomib exposure (BE) will be calculated. At each visit, patients will be assessed clinically for the side effects of bortezomib (peripheral neuropathy, myelosuppression, gastrointestinal disturbance) and dexamethasone (cushingoid features, weight gain, pedal edema, cataracts, glaucoma, sleep, and behaviour changes). Treatment interruptions for side effects will be allowed at the physician’s discretion.  
Comparator Agent  NIL  NIL 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  60.00 Year(s)
Gender  Both 
Details  Adult patients 18 to 60 years of age and of either sex diagnosed with wAIHA (idiopathic, or secondary to an autoimmune disorder) who are relapsed, or refractory (RR) to prednisolone and single agent rituximab as first and second-line therapies, respectively and require initiation of third-line treatment will be included.  
 
ExclusionCriteria 
Details  Patients with wAIHA less than 18 years of age, wAIHA secondary to a lymphoproliferative disorder and those unwilling to participate in the study will be excluded 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
Efficacy (Response rates) and safety of bortezomib-dexamethasone as third-line therapy in wAIHA.  1-month, 3-months, 6-months, 1-year 
 
Secondary Outcome  
Outcome  TimePoints 
Feasibility of achieving a treatment-free remission (TFR) after bortezomib discontinuation.  6-months, 1-year and 2-years 
 
Target Sample Size   Total Sample Size="5"
Sample Size from India="5" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   01/04/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Yet Recruiting 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - YES
  1. What data in particular will be shared?
    Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).

  2. What additional supporting information will be shared?
    Response -  Study Protocol
    Response -  Statistical Analysis Plan
    Response - Informed Consent Form
    Response - Clinical Study Report

  3. Who will be able to view these files?
    Response - Researchers who provide a methodologically sound proposal.

  4. For what types of analyses will this data be available?
    Response - To achieve aims in the approved proposal.

  5. By what mechanism will data be made available?
    Response - Proposals should be directed to [drankur589@yahoo.in].

  6. For how long will this data be available start date provided 01-02-2026 and end date provided 01-02-2031?
    Response - Beginning 3 months and ending 5 years following article publication.

  7. Any URL or additional information regarding plan/policy for sharing IPD? 
    Additional Information - NIL
Brief Summary  
Introduction

Warm autoimmune hemolytic anaemia (wAIHA) is a rare disease with an estimated annual incidence of  5-10 per 100,000 population. It is characterized by hemolysis with a strongly positive direct agglutination test for IgG + C3d. It is a chronic condition with frequent relapses and a need for multiple treatment lines to sustain transfusion independence. Despite high initial responses with the first 2 treatment lines (corticosteroids and rituximab), relapses are frequent. For third-line and later, immunosuppressive (IS) drugs (azathioprine, mycophenolate mofetil, cyclosporine) and splenectomy are the available options, albeit with an increased risk of life-threatening infections. Anti-plasma cell therapies (bortezomib, daratumumab) in combination with dexamethasone target long-term memory B-cells and plasma cells resulting in a reduction of the autoantibody production. Bortezomib has shown promising preclinical activity in autoimmune disorders like systemic lupus erythematosus (SLE) and immune thrombocytopenia. Anecdotal case reports and retrospective case series indicate the efficacy of bortezomib in both warm and cold AIHA. In the present study, we prospectively evaluated the efficacy, safety, and feasibility of achieving treatment-free remission (TFR) with weekly bortezomib- dexamethasone in patients with wAIHA in the third-line setting as an alternative to IS drugs and splenectomy.

Study Objectives:

1.   To evaluate the efficacy and safety of bortezomib-dexamethasone as a third-line therapy in patients with warm autoimmune hemolytic anaemia 

2. To assess the feasibility of achieving a treatment-free remission (TFR) after bortezomib  discontinuation

Methods

This prospective pilot study will be conducted in the department of haematology of the Safdarjung hospital, New Delhi. Five adult patients 18-60 years of age 18 and of either sex diagnosed with wAIHA (idiopathic, or secondary to an autoimmune disorder) who were relapsed, or refractory (RR) to prednisolone and single agent rituximab as first and second-line therapies, respectively and require initiation of third-line treatment will be included. Patients with wAIHA less than 18 years of age, wAIHA secondary to a lymphoproliferative disorder (LPD) and those unwilling to participate in the study will be excluded. Per protocol, patients will be treated with bortezomib- 1.3 mg/m2 subcutaneously/week and dexamethasone- 40 mg per oral/week (Vd, 4 weeks=1 cycle). Acyclovir (400 mg twice a day) will be used as prophylaxis for herpes zoster reactivation during treatment and until 3 months following bortezomib discontinuation. Initially, weekly assessments will be done with complete blood count, corrected reticulocyte count, serum lactate dehydrogenase (LDH), and liver function tests till partial response (PR), after which, the frequency of testing will be reduced to monthly intervals, or earlier, in case of clinical suspicion of relapse (worsening dyspnea, fatigue). Once sustained complete response (CR) was achieved with weekly Vd, treatment will be gradually tapered in an attempt to achieve TFR. During tapering, Vd will be administered once every 2-weeks (2-weekly Vd). For patients relapsing on 2-weekly Vd, treatment will be changed to Vd-lite (bortezomib-1.3 mg/m2 subcutaneous/week and dexamethasone-20 mg/week, 4- weeks=1 cycle). Treatment will be discontinued once sustained CR is achieved with either 2-weekly Vd, or Vd-lite. Patients will be followed up for a minimum of 1 year. Responses will be recorded as PR, CR, sustained CR, and no response (NR) and duration of response (DOR), and bortezomib exposure (BE) will be calculated. At each visit, patients will be assessed clinically for the side effects of bortezomib (peripheral neuropathy, myelosuppression, gastrointestinal disturbance) and dexamethasone (cushingoid features, weight gain, pedal edema, cataracts, glaucoma, sleep, and behaviour changes). Treatment interruptions for side effects will be allowed at the physician’s discretion. Results will be reported using descriptive analysis and compared with the available literature.
 
Close