| CTRI Number |
CTRI/2025/07/090198 [Registered on: 04/07/2025] Trial Registered Prospectively |
| Last Modified On: |
02/07/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
To study safety and efficacy of Romiplostim in addition to immunosuppressive ATG and CSA therapy as the first line of therapy compared to ACE ATG and CSA and ELT therapy in Indian Aplastic Anemia patients |
|
Scientific Title of Study
|
Randomised Controlled Trial of immunosuppressive therapy ATG+CSA with Eltrombopag ACE and ATG+CSA with Romiplostim in Aplastic Anemia & correlation of therapy response with transcriptomic profiling. |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 51/05/2024/NCD/HB/NIIH |
Other |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Chandrakala Shanmukhaiah |
| Designation |
Professor and Head |
| Affiliation |
Seth GS Medical College and KEM Hospital |
| Address |
Department of Clinical Hematology
10th Floor Ward no 42
Room number 1002
Multistorey Building
Seth GS Medical College and KEM Hospital
Acharya Donde Marg
Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
|
| Fax |
|
| Email |
drchandra1s@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Babu Rao Vundinti |
| Designation |
Scientist G and Deputy Director |
| Affiliation |
ICMR National Institute of Immunohaematology |
| Address |
ICMR National Institute of Immunohaematology
13th Floor Multi storey Building
Seth GS Medical College and KEM Hospital
Acharya Donde Marg
Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
02224138519 |
| Fax |
|
| Email |
vbaburao@hotmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Chandrakala Shanmukhaiah |
| Designation |
Professor & Head |
| Affiliation |
Seth GS Medical College and KEM Hospital |
| Address |
Department of Clinical Hematology
10th floor, ward no. 42, room no.1002, Multistorey building, Seth GS Medical College and KEM Hospital
Acharya Donde Marg
Parel
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9699087654 |
| Fax |
|
| Email |
drchandra1s@gmail.com |
|
|
Source of Monetary or Material Support
|
| INDIAN COUNCIL OF MEDICAL RESEARCH |
|
|
Primary Sponsor
|
| Name |
Indian Council of Medical Research- National Institute of Immunohaematology |
| Address |
13th Floor, Multi-storey Building, Seth GS Medical College and KEM Hospital,
Acharya Donde Marg, Parel, Mumbai- 400012
|
| Type of Sponsor |
Research institution |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 2 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Babu Rao Vundinti |
ICMR-NATIONAL INSTITUTE OF IMMUNOHAEMATOLOGY |
13th Floor, Multi-storey Building, Seth GS Medical College and KEM Hospital,
Acharya Donde Marg, Parel, Mumbai- 400012
Mumbai
MAHARASHTRA |
9892463778
vbaburao@hotmail.com |
| Dr Chandrakala Shanmukhaiah |
Seth GS Medical College and KEM Hospital |
Department of Clinical Haematology,
10th Floor, Ward no. 42, Room number 1002,
Multi-storey Building, Seth GS Medical College and KEM Hospital,
Acharya Donde Marg, Parel, Mumbai- 400012
Mumbai
MAHARASHTRA |
9699087654
drchandra1s@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 2 |
| Name of Committee |
Approval Status |
| INSTITUTIONAL ETHICS COMMITTEE (IEC)-I |
Approved |
| Institutional Ethics Committee for Research on Human Subjects |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D618||Other specified aplastic anemias and other bone marrow failure syndromes, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Antithymocyte globulin (ATG) + Cyclosporine A(CSA) + Eltrombopag |
Immunosuppression ATG 40mg/kg/day for 4 days, Cyclosporine 5 mg/kg/day for 6 to 12 months and Eltrombopag 150 mg per day for 6 months |
| Intervention |
Antithymocyte globulin (ATG)+Cyclosporine A(CSA)+Romiplostim |
Immunosuppression ATG 40mg/kg/day for 4 days, Cyclosporine 5 mg/kg/day for 6 to 12 months and Romiplostim 10 µgm/kg/week for 6 months. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
45.00 Year(s) |
| Gender |
Both |
| Details |
Newly diagnosed acquired AA patients (Patients with hypocellular marrow i.e Less than 25% marrow cellularity; peripheral blood pancytopenia) of any gender aged 18 years to 45 years, willing for consent and follow up will be recruited for the study.
Negative for chromosomal breakages in MMC induced peripheral blood culture (negative for Fanconi’s anemia).
Willing to follow the study protocol.
No history of infections, chemical exposure or radiation therapy.
Treatment naive AA.
ECOG performance status 1-2
|
|
| ExclusionCriteria |
| Details |
Aplastic anemia patients positive for chromosomal breakages in PHA stimulated, MMC induced peripheral blood cultures and other inherited bone marrow failure syndromes.
Secondary marrow aplasia (secondary to HSCT, drug or chemical exposure, radiotherapy, hepatitis),
Patients with MDS
Aplastic anemia Patients planning for HSCT.
History of allergy to the drug ingredients.
Participating in other drug clinical trials in the past 1 month.
Known case of Human Immunodeficiency Virus, active Hepatitis C infection or Hepatitis B infection.
Women who are pregnant or breast feeding or women of childbearing potential not willing to follow double contraceptive measures.
Any other reason that in the opinion of the investigator is likely to cause harm to the participant or will adversely affect the results of the study.
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
On-site computer system |
|
Blinding/Masking
|
Outcome Assessor Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
The study will establish safety of combine therapy of ROM and IST vs ELT and IST as first line of therapy in Indian AA.
Proportion of patients with complete response (CR) (hematological CR defined by hemoglobin level more than 10 g/dL, absolute neutrophil count more than 1000 and platelets more than 100 X109 cells/L)
Proportion of patients with partial response (PR) (PR defined as no longer meeting the criteria for SAA and transfusion independency with hemoglobin level more than 8 g/dL, absolute neutrophil count than 500, and platelet count more than20 X 109/L).
Proportion of Non-responder (NR)(NR defined as any patient not meeting any of the response criteria defined above).
|
Time from recruitment to the primary outcome will be 6 months followed by 3 months follow up. |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The study will identify a differential gene expression pattern in AA patients treated with
TPO-R agonist (ELT or ROM) in combination with IST. |
3 Years |
Identification of prime biomarkers in responders and non-responders at the time of
diagnosis. |
3 Years |
Correlation of genomic changes and expression profile of AA patients with response and
non-response to the therapy. |
3 Years |
To correlate response-based reticulocyte count, PNH clone, lineage specific differential
gene expression pattern identified through ScRNA seq. |
3 Years |
| Hematological profile at 3, 6 and 12 months. |
3,6 and 12 months |
Volume of blood and platelets transfused at the end of 3, 6 and 12 months (in case of
transfusion dependence). |
3,6 and 12 months |
| To correlate the trough concentrations of ROM+IST with safety and efficacy parameters |
3 Years |
Change in quality of life at 6 months as assessed by Transfusion-dependent Quality of Life
(TranQoL) questionnaire and the European Organization for Research and Treatment of
Cancer (EORTC) Quality of Life Questionnaire (QLQ) scores |
6 months |
Incidence of treatment emergent adverse events [TEAEs] of grade 3 or more severity at 12
months [As per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
dated 27 November 2017] |
12 months |
|
|
Target Sample Size
|
Total Sample Size="50"
Sample Size from India="50"
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
|
N/A |
|
Date of First Enrollment (India)
|
15/04/2026 |
| 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="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| 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 - NO
|
|
Brief Summary
|
Aplastic Anemia (AA) can be treated with Hematopoietic Stem cells transplantation (HSCT) and Immune suppressive therapy (IST) but a lack of suitable donors and side effects of the drug impact the management of the study. Routinely, Antithymocyte globulin (ATG), Cyclosporine A (CSA) and Eltrombopag (ELT) known as ACE therapy is used in the treatment of AA, Long-term follow-up studies have reported hepatotoxicity in the subjects treated with Eltrombopag.
Romiplostim (ROM) in later studies have shown a good response in Immune thrombocytopenia (ITP) subjects and is well tolerated in AA subjects. However, its efficacy as a first-line treatment in combination with IST remains unexplored. A pilot study from India reported an effective response from ROM+ ATG + CSA in AA as first line therapy. This combination thus needs further evaluation with a large sample size and defined class of AA. Hence we have proposed to study AA subjects with the objectives of treatment two regimen (a) ATG+CSA+ELT (N=25) and (b) ATG+CSA+ROM (N=25), with follow up at 3 months, 6 months and 12 months. The genomic and transcriptomic changes are identified through next generation sequencing (NGS). The expected outcome of the study will measure the proportions of complete response (CR), Partial response (PR) and no response (NR). The study will also be establishing response rate of ROM+ATG +CSA as the first line therapy. Additionally, study will aid to understand the diverse transcriptomic patterns in responders and non-responder responsible for heterogeneity in BMF. |