| CTRI Number |
CTRI/2024/12/078656 [Registered on: 27/12/2024] Trial Registered Prospectively |
| Last Modified On: |
26/12/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Non-randomized, Active Controlled Trial |
|
Public Title of Study
|
Treatment of bone marrow related disease with aresnic trioxide and artesnuate |
|
Scientific Title of Study
|
Targeting metabolic vulnerability of BCR: ABL negative myeloproliferative neoplasms: Focus on Primary Myelofibrosis. |
| Trial Acronym |
NA |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NOT APPLICABLE |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore Ranipet campus |
| Address |
Room no-26, 5th Floor, A Block,
Department of Haematology
Vellore
TAMIL NADU
632517
India |
| Phone |
914172224480 |
| Fax |
04172-224480 |
| Email |
vikram@cmcvellore.ac.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore Ranipet campus |
| Address |
Room no-26, 5th Floor, A Block,
Department of Haematology
TAMIL NADU
632517
India |
| Phone |
914172224480 |
| Fax |
04172-224480 |
| Email |
vikram@cmcvellore.ac.in |
|
Details of Contact Person
Public Query
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Vellore Ranipet campus |
| Address |
Room no-26, 5th Floor, A Block,
Department of Haematology
TAMIL NADU
632517
India |
| Phone |
914172224480 |
| Fax |
04172-224480 |
| Email |
vikram@cmcvellore.ac.in |
|
|
Source of Monetary or Material Support
|
| Indian council of medical research,
V. Ramalingaswami Bhawan, P.O. Box No. 4911Ansari Nagar, New Delhi - 110029, India |
|
|
Primary Sponsor
|
| Name |
Indian council of medical research |
| Address |
V. Ramalingaswami Bhawan,
P.O. Box No. 4911
Ansari Nagar,
New Delhi - 110029 |
| Type of Sponsor |
Other [Charitable trust hospital] |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Not applicable |
Not applicable |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Vikram Mathews |
Christian Medical College Vellore Ranipet campus |
Department of Haematology,
Room 26, 5TH Floor, A Block
Vellore
TAMIL NADU |
91417224480
91417224480
vikram@cmcvellore.ac.in |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Review Boaard |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C96Z||Other specified malignant neoplasms of lymphoid, hematopoietic and related tissue, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Cohort 2:
Injection Arsenic trioxide (ATO)
Injection Artesunate (ART) |
Injection ATO 10 mg IV for
10 days
Injection ART at 2.4 mg/kg/day for 14 days |
| Intervention |
Cohort-1:
Injection Arsenic trioxide (ATO) Injection Artesunate (ART) |
Injection ATO 10 mg IV x 10 days
Injection artesunate (ART) starting at 2.4mg/kg/day x 7 days |
| Intervention |
Cohort-3:
Injection Arsenic trioxide (ATO) Injection Artesunate (ART) |
Injection ATO 10 mg IV for 10 days
Injection ART at 4 mg/kg/day for 14 days |
| Comparator Agent |
Not applicable |
Not applicable |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
Subjects age ≥ 18 years of age (adults)
Subjects must be diagnosed with Primary Myelofibrosis according to the 2008 World Health Organization criteria (Table 2 in Tefferi and Vardiman, 2008) irrespective of JAK2 mutation status.
Subjects with an ECOG performance status of 0, 1, or 2.
Subjects with peripheral blood blast count of less than 10% at the Screening and Baseline visits. |
|
| ExclusionCriteria |
| Details |
Subjects with a life expectancy of less than six months.
Subjects in whom MF disease is well controlled with current therapy.
Females who are pregnant or are currently breastfeeding.
Subjects of childbearing potential who are unwilling to take appropriate precautions (from Screening through Follow-up) to avoid becoming pregnant or fathering a child.
Subjects with inadequate bone marrow reserve as demonstrated by:
a. Absolute neutrophil count (ANC) that is less than 500
b. Platelet count less than 30,000 without the assistance of growth factors, thrombopoietic factors, or platelet transfusions. Subjects must not have received growth factors for at least one month before receiving the first dose of the study drug.
6. Subjects with inadequate liver or renal function as demonstrated by:
a. Direct bilirubin above 2 X upper limit of laboratory normal (ULN). (NOTE:
Direct bilirubin will only be determined if total bilirubin is above 2.0 x ULN).
b. Alanine aminotransferase (ALT) above 2.5x upper limit of laboratory normal
(ULN). |
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of subjects achieving above 35% reduction in spleen volume from baseline to Week 24 as measured by ultrasound (or CT scan in applicable subjects) |
Assessed at 3 months 6 months and at 1 year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Duration of maintenance of a above 35% reduction from baseline in spleen volume among subjects receiving intervention.
Proportion of subjects who have above 50% reduction in total symptom score from baseline to Week 24 as measured by the Modified MFSAF.
• Reduction in JAK2V617F allelic burden in those who are positive at diagnosis
• Overall survival. |
Assessed at 3 months, 6 months and 12 months |
|
|
Target Sample Size
|
Total Sample Size="25"
Sample Size from India="25"
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 1/ Phase 2 |
|
Date of First Enrollment (India)
|
08/01/2025 |
| 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 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
|
Aim
To
target the metabolic vulnerability of BCR: ABL negative myeloproliferative
neoplasms: Focus on Primary Myelofibrosis
Patients and Methods:
Early phase
II open-labeled single arm study design will be utilized to study the impact of
arsenic trioxide and artesunate on PMF. Patients with advanced disease
scheduled to start treatment with Ruxolitinib or to undergo an alloHCT will be
given a 6-month course of the novel intervention after validation of the
findings before those mentioned above, as well as more standard interventions
to assess response.
This exploratory
early-phase trial will enroll 25 patients over two years.
Expected outcome:
The proposed study aims to validate
the metabolic and phenotypic vulnerabilities of JAK2 V617F+ cells using
FDA-approved drugs and novel drug combinations. This study will also determine
the effect of promising drugs on bone marrow fibrosis in PMF. This would have
the potential to translate into a novel therapeutic strategy in the clinical
management of PMF, which otherwise does not have therapies that alter the
clinical course of the disease.
|