| CTRI Number |
CTRI/2024/05/067949 [Registered on: 27/05/2024] Trial Registered Prospectively |
| Last Modified On: |
23/10/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Phase II study for testing Leflunomide to Prevent Cytomegalovirus (CMV) Reactivation in Stem Cell Transplant Patients |
|
Scientific Title of Study
|
Use of Leflunomide as Primary Prophylaxis against Cytomegalovirus (CMV) Reactivation in Haploidentical Haematopoietic Stem Cell Transplant (HIT) Single arm Phase 2 Clinical Trial
|
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| Study protocol Version 1.1 dated 22/02/2024 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Lingaraj Nayak |
| Designation |
Professor and Medical Oncology |
| Affiliation |
ACTREC Tata Memorial Centre |
| Address |
Department of adult haematolymphoid and BMT room no 103 and 307 shanti sadan opd sector 22 cisf road owe camp kharghar navi mumbai
Raigarh
MAHARASHTRA
410210
India |
| Phone |
9167294976 |
| Fax |
|
| Email |
lingarajnayak86@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Lingaraj Nayak |
| Designation |
Professor and Medical Oncology |
| Affiliation |
ACTREC Tata Memorial Centre |
| Address |
Department of adult haematolymphoid and BMT room no 103 and 307 shanti sadan opd sector 22 cisf road owe camp kharghar navi mumbai
Raigarh
MAHARASHTRA
410210
India |
| Phone |
9167294976 |
| Fax |
|
| Email |
lingarajnayak86@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Lingaraj Nayak |
| Designation |
Professor and Medical Oncology |
| Affiliation |
ACTREC Tata Memorial Centre |
| Address |
Department of adult haematolymphoid and BMT room no 103 and 307 shanti sadan opd sector 22 cisf road owe camp kharghar navi mumbai
Raigarh
MAHARASHTRA
410210
India |
| Phone |
9167294976 |
| Fax |
|
| Email |
lingarajnayak86@gmail.com |
|
|
Source of Monetary or Material Support
|
| Extramural ICMR V. Ramalingaswami Bhawan, P.O. Box No. 4911
Ansari Nagar, New Delhi 110029, India |
|
|
Primary Sponsor
|
| Name |
Tata Memorial Hospital |
| Address |
Dr Ernest Borges Marg Parel Mumbai 400012 |
| Type of Sponsor |
Research institution and hospital |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Lingaraj Nayak |
Advanced Centre for Treatment Research and Education in Cancer Tata Memorial centre |
Department of adult haematolymphoid and BMT room no 103 and 307 shanti sadan opd sector 22 cisf road owe camp kharghar navi mumbai
Raigarh
MAHARASHTRA |
9167294976
lingarajnayak86@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee ACTREC IEC III |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C969||Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified, (2) ICD-10 Condition: Z949||Transplanted organ and tissue status, unspecified, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Leflunomide |
Patients in study shall receive loading dose of Tab Leflunomide 100 mg daily for 3 days
followed by 20 mg daily orally. Leflunomide will be given till day 180 + post haplo-HSCT or
till patient is on systemic immunosuppression |
| Comparator Agent |
Not Applicable |
Not Applicable |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
- Males or females undergoing Haplo-identical haematopoetic stem cell transplant.
-Undetectable CMV from plasma sample in preceding 7 days
-Patient who has WBC engraftment ANC More than 500 per cu mm for 3 or more consecutive
days.
-Within 7 days of WBC engraftment
-Adequate liver functions ALT or AST less than 5 times upper limit of normal and
Bilirubin less than 3 times upper limit of normal at time of starting leflunomide
-Understands the study procedures, alternative treatment available and risks involved
with the study and voluntarily agree to participate by giving written informed
consent.
|
|
| ExclusionCriteria |
| Details |
-Known hypersensitivity to Leflunomide
-History of clinically significant CMV reactivation in past 1 year
-Patient is receiving or has received drug known to have anti CMV activity within in last
7 days Ganciclovir, valganciclovir, foscarnet, letermovir, acyclovir at doses more than 3200
mg PO per day or more than 25 mg/kg IV per day), valacyclovir (at doses More than 3000 mg PO per day
-Inadequate renal function creatinine clearance less than 30 ml per min
-Chronic active hepatitis B (HBsAg+ or any HBV DNA+), hepatitis C, or/& HIV
-Any psychiatric condition that might limit the ability of the patient to comply with the
protocol |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To determine the rate of clinically significant CMV infection on prophylactic leflunomide in
haplo-HSCT patients till day+180 post HSCT
|
25 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
-To evaluate the safety of post-transplant leflunomide using
-To evaluate the incidence of clinically significant BK virus
reactivation in peripheral blood and urine till day+180 Clinically significant BK virus reactivation will be defined as per ECIL-6
guidelines as more than 107 copies more than 7 log 10 gEq per mL in urine and
103 copies more than 1000 gEq per mL in blood will be considered significant
thresholds to define BK virus re-activation
- To evaluate the incidence of grade III IV acute GVHD.
|
5 years |
|
|
Target Sample Size
|
Total Sample Size="22"
Sample Size from India="22"
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)
|
03/06/2024 |
| 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="5"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Background
Allogeneic hematopoietic
stem cell transplantation (allo-HSCT) is an established therapy for a variety
of malignancies, congenital and acquired hematological diseases as well as
immunodeficiencies . Allo-HSCT can be broadly classified into 3 types – matched
related donor (MRD) (includes matched sibling donor) transplants, unrelated
donors and haploidentical (haplo) transplants. Severe viral infections are more
common after unrelated donor allo-HSCT, and after haplo-HSCT. Viral infections
account for a large part of complications and even fatalities after HSCT. While
hygienic measures and patient isolation protect against some pathogens, a special
risk originates from viruses that silently persist within the patient or the
transplanted cells. After primary infection, viruses like Epstein-Barr virus
(EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), adenovirus (ADV),
herpes simplex virus (HSV) and varicella zoster virus (VZV) can reactivate
especially in the context of immunodeficiency and immunosuppression . B-cell
function and specific antibodies are important for defence against infection
with exogenous viruses, while cytotoxic T-cells are important for preventing
severe viral disease and against latent viruses. The immune defects in
HSCT-patients are frequently complex with defects in cytotoxic T-lymphocyte,
helper T-lymphocyte, NK-cell, and B-lymphocyte functions Rationale for dose Dose of leflunomide used in this study will be 100mg OD for 3 days followed by 20mg OD.
This is based on the standard approved dose of leflunomide used in Rheumatoid arthritis and our prior experience with leflunomide in treatment of CMV Rationale for duration Most haplo-HSCT patients have CMV reactivation within first 3 months (day +100) posttransplant. Marty et al also used letermovir prophylaxis for 100 days post-transplant. However,
there is a concern for delayed CMV disease after stoppage of prophylaxis . As leflunomide
is a safe drug and can be used for prolonged duration, we will use leflunomide for 180 days
post-transplant or until the patient is on immunosuppression i.e., calcineurin inhibitor (CNI),
mycophenolate mofetil (MMF), Etanercept, Ruxolitinib or steroid (above the replacement dose
of 7.5 mg prednisolone), whichever is later |