| CTRI Number |
CTRI/2024/03/063966 [Registered on: 11/03/2024] Trial Registered Prospectively |
| Last Modified On: |
10/08/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
Romiplostim in Inherited marrow failure syndromes - Safety and Efficacy |
|
Scientific Title of Study
|
‘An Open-Label, Single-Arm
Interventional Study to Evaluate the Safety and Efficacy of Romiplostim in Danazol
Resistant/ Intolerant Inherited Bone Marrow Failure Syndromes’ |
| Trial Acronym |
RISE |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 2023-19976 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Aruna Rajendran |
| Designation |
Assistant professor |
| Affiliation |
Madras Medical College |
| Address |
Room no 246 B,4th floor, Tower 2, Bone Marrow Transplant Unit, Department of Hematology, Rajiv Gandhi Government Hospital, Park Town, Opposite to Central Railway Station, Chennai
Chennai
TAMIL NADU
600003
India |
| Phone |
9500008770 |
| Fax |
|
| Email |
drarunasasidaran@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Aruna Rajendran |
| Designation |
Assistant professor |
| Affiliation |
Madras Medical College |
| Address |
Room no 246 B,4th floor, Tower 2, Bone Marrow Transplant Unit, Department of Hematology, Rajiv Gandhi Government Hospital, Park Town, Opposite to Central Railway Station, Chennai
Chennai
TAMIL NADU
600003
India |
| Phone |
9500008770 |
| Fax |
|
| Email |
drarunasasidaran@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Aruna Rajendran |
| Designation |
Assistant professor |
| Affiliation |
Madras Medical College |
| Address |
Room no 246 B,4th floor, Tower 2, Bone Marrow Transplant Unit, Department of Hematology, Rajiv Gandhi Government Hospital, Park Town, Opposite to Central Railway Station, Chennai
Chennai
TAMIL NADU
600003
India |
| Phone |
9500008770 |
| Fax |
|
| Email |
drarunasasidaran@gmail.com |
|
|
Source of Monetary or Material Support
|
| INDIAN COUNCIL OF MEDICAL RESEARCH |
|
|
Primary Sponsor
|
| Name |
INDIAN COUNCIL OF MEDICAL RESEARCH |
| Address |
V. Ramalingaswami Bhawan, P.O. Box No. 4911
Ansari Nagar, New Delhi - 110029, India |
| Type of Sponsor |
Government funding agency |
|
|
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 Aruna Rajendran |
Madras Medical College |
Room no 246 B,4th floor, Tower 2, Bone Marrow Transplant Unit, Department of Hematology, Rajiv Gandhi Government Hospital, Park Town, Opposite to Central Railway Station, Chennai- 600003
Chennai
TAMIL NADU |
9500008770
drarunasasidaran@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethical Committee Madras Medical College |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D610||Constitutional aplastic anemia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Inj Romiplostim |
Study Drug Inj Romiplostim, a thrombopoietin Receptor agonist, will be administered subcutaneously on weekly basis starting at the dose of 3mcg per kg and escalated by 1mcg per kg per week to reach a ceiling dose of 10 mcg per kg per week on week 8 and continued till week 24 or week 12 based on hematological response |
| Comparator Agent |
not applicable |
not applicable |
|
|
Inclusion Criteria
|
| Age From |
2.00 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
Patients with IBMFS including Fanconi anemia, dyskeratosis congenita causing cytopenias Hb less than 8 gram per decilitre, ANC less than 500 cells or Platelet count less than 30,000 per microlitre or bone marrow cellularity less than 25 percent and with danazol resistance or intolerance |
|
| ExclusionCriteria |
| Details |
Known hypersensitivity or past use of Romiplostim, history of thrombosis, patients with IBMF with co-existing myelodysplasia or malignancies and organ dysfunction; presence of FANCD mutation
|
|
|
Method of Generating Random Sequence
|
|
|
Method of Concealment
|
|
|
Blinding/Masking
|
|
|
Primary Outcome
|
| Outcome |
TimePoints |
A. Twenty five percent reduction in transfusion requirement compared to baseline
B. Achieving platelet count more than 30,000 per microlitre, Hb more than 8gram per decilitre or ANC more than 500 per microlitre compared to baseline
C. Transfusion independence for 4 consecutive weeks
D. Bone marrow response, defined as an increase in bone marrow cellularity by at least two-fold from baseline.
|
12 and 24 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The following known drug related adverse reactions will be monitored
1. Occurrence of clonal evolution
2. Thrombotic events
3. Allergy/ hypersensitivity
4. Pain at injection site
5. Headache
6. Myalgia
7. Fatigue
8. Dizziness
9. Transaminitis
10. Any other symptom reported by the patient up to 4 weeks after study completion.
Along with disease related adverse events like
1. Infection
2. Anemia
3. Bleeding
|
weekly basis from week 1 to week 36 |
|
|
Target Sample Size
|
Total Sample Size="10"
Sample Size from India="10"
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="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| 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
|
This interventional pilot study proposes to evaluate the efficacy and safety of repurposed drug Romiplostim in children with inherited bone marrow failure syndromes (IBMFS), namely Fanconi anemia and Dyskeratosis Congenita who are Danazol resistant/ intolerant and are pancytopenic as a non-transplant medical therapy in patients who are transplant ineligible or do not have HLA matched related or unrelated donor. Primary Objective: To study the effectiveness of romiplostim to reduce transfusion requirement or improve bone marrow cellularity in patients with IBMFs at week 24 of therapy. Secondary Objectives: 1. To monitor for adverse events in use of Romiplostim for patients with IBMFS 2. To evaluate the effectiveness of Romiplostim in achieving transfusion independence in patients with IBMFS at week 24 of therapy 3. To identify the genetic mutations seen in patients with Danazol resistant IBMFS. Primary endpoint: To evaluate efficacy of the drug defined as any one or more of following primary responses. A. Twenty Five percent reduction in transfusion requirement compared to baseline or B. Achieving platelet count more than 30,000 per microlitre, Hb more than 8 gram per decilitre or ANC more than 500 per microlitre or C. Transfusion independence for 4 consecutive weeks or D. Bone marrow response, defined as an increase in bone marrow cellularity by at least two-fold from baseline at either of time points of assessment (Week 12 in patients with no hematological response & week 24 in all patients). Secondary Endpoints: 1. To evaluate drug related and disease related adverse events 2. To evaluate the percentage of study participants who achieve transfusion independence during the study period. 3.To identify the genetic mutations seen in patients with Danazol resistant IBMFS. Sample size is 10 participants with danazol resistant / intolerant IBFMS. Study Subjects: Children between the age of 2 to 18 years (inclusive of 2 years and 18 years). Study site: Madras Medical College Children with Danazol resistant/ intolerant IBMFS will undergo baseline marrow evaluation to rule out Myelodysplastic syndromes. They will also undergo genetic studies to identify disease causing mutation. Children fulfilling eligibility criteria and after informed consent, will be administered study drug Inj Romiplostim initially at dose of 3mcg/kg/week subcutaneously (week 1) and escalated every week by 1 mcg/kg/week (week 8) to reach a ceiling dose of 10 mcg/kg/week and continued in that dose till week 12. Their response to therapy will be monitored with weekly blood counts and any adverse events will be monitored. The study duration is 36 months . |