| CTRI Number |
CTRI/2024/03/063617 [Registered on: 05/03/2024] Trial Registered Prospectively |
| Last Modified On: |
04/03/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A study to find new treatments for patients with blood cancers |
|
Scientific Title of Study
|
Novel and optimized de-intensified induction therapy in acute myeloid leukemia. |
| Trial Acronym |
NADIRx |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| Nil |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Ranipet Campus |
| Address |
Room no-26, A Block, 5th Floor, Department of Haematology, Christian Medical College Ranipet Campus, Ranipet
Vellore
TAMIL NADU
632517
India |
| Phone |
04172224480 |
| Fax |
04172224480 |
| Email |
vikram@cmcvellore.ac.in |
|
Details of Contact Person
Scientific Query
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Ranipet Campus |
| Address |
Room no-26, A Block, 5th Floor, Department of Haematology, Christian Medical College Ranipet Campus, Ranipet
TAMIL NADU
632517
India |
| Phone |
04172224480 |
| Fax |
04172224480 |
| Email |
vikram@cmcvellore.ac.in |
|
Details of Contact Person
Public Query
|
| Name |
Vikram Mathews |
| Designation |
Professor |
| Affiliation |
Christian Medical College Ranipet Campus |
| Address |
Room no-26, A Block, 5th Floor, Department of Haematology, Christian Medical College Ranipet Campus, Ranipet
TAMIL NADU
632517
India |
| Phone |
04172224480 |
| Fax |
04172224480 |
| Email |
vikram@cmcvellore.ac.in |
|
|
Source of Monetary or Material Support
|
| India Alliance DBT Wellcome |
|
|
Primary Sponsor
|
| Name |
India Alliance DBT Wellcome |
| Address |
Nishant House, 8-2-351/N/1, 2nd floor, Road No.2,Venkateshwara Hills, Banjara Hills, Hyderabad - 500034 |
| 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 = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Vikram Mathews |
Christian Medical College Vellore Ranipet Campus |
A501, Department of Haematology, Christian Medical College Vellore Ranipet campus
Vellore
TAMIL NADU |
04172224480
04172224480
vikram@cmcvellore.ac.in |
| Smita Kayal |
Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER Campus) |
Department of Medical Oncology,
Dhanvantari Nagar
Pondicherry
PONDICHERRY |
07598118439
07598118439
kayalsmita@gmail.com |
| Manju Sengar |
Tata Memorial Center |
Tata Memorial Center
Department of Medical Oncology
Mumbai
MAHARASHTRA |
09769690590
09769690590
manju.sengar@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: D758||Other specified diseases of bloodand blood-forming organs, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
For Phase 2
Inj Azacytidine
Tab Venetoclax |
Inj Azacytidine 75mg/m2 per day for 7 days
Tab Venetoclax 100mg per day for 14 days
|
| Intervention |
Phase-1: Cohort-1
Inj Azacytidine
Inj Artesunate |
Inj Azacytidine x 75mg/m2 per day for 7 days
Inj Artesunate x 2.4mg/kg per day x 7 days
the above will be repeated for every 28 days for 4 cycles |
| Intervention |
Phase-1: Cohort-2:
Inj Azacytidine
Inj. Artesunate
Inj. Arsenic trioxide |
Inj Azacytidine 75mg/m2 per day for 7days
Inj. Artesunate 2.4mg/kg per day for 7 days
Inj. Arsenic trioxide 10mg per day for 14 days.
The above will be repeated every 28 days for 4 cycles. |
| Intervention |
Phase-1: Cohort-3:
Inj Azacytidine
Inj Artesunate
Inj Arsenic trioxide |
Inj Azacytidine 75mg/m2 per day for 7days
Inj. Artesunate 4mg/kg per day for 14 days
Inj. Arsenic trioxide 10mg per day for 14 days.
The above will be repeated every 28 days for 4 cycles. |
| Intervention |
Recommended dose and schedule informed from Phase I study |
Recommended dose and schedule informed from Phase I study |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Both |
| Details |
Aged above 18 years of age
Newly diagnosed de-novo acute myeloid leukaemia.
ECOG performance score above 2 Adequate renal function: Glomerular Filtration Rate above 60ml/min
Adequate hepatobiliary function: Total bilirubin less than 2 x Upper limit normal
Adequate cardiac function with no past history of ischaemic heart disease and normal ejection fraction
Female participants of child bearing potential must have a negative pregnancy test less than 72 hours prior to initiating study intervention and agree to avoid pregnancy using adequate, medically approved contraceptive precautions for up to 6 weeks after the last dose of study treatment intervention
Male participants with a partner of childbearing potential must agree to use adequate, medically approved contraceptive precautions during and for up to 6 weeks after the last dose of the study treatment intervention
Patient able and willing to provide written, informed consent for the study. |
|
| ExclusionCriteria |
| Details |
Contraindication to the use of arsenic trioxide or artesunate due to hypersensitivity or past history of adverse events with these agents, or any other medical contraindication to administer these drugs
Pregnancy or lactation
Male or female participants unwilling to use an effective method of birth control (either hormonal in the form of the contraceptive pill or barrier method of birth control accompanied by the use of a proprietary spermicidal foam/gel or film); or agreement of true abstinence from time consent is signed until 6 weeks after the last dose of study treatment intervention (i.e. withdrawal, calendar, ovulation, symptothermal and post ovulation methods are not considered acceptable methods)
4. Evidence of sepsis with hemodynamic compromise at diagnosis
History of immunosuppression
History of hearing or balance problems
Any other malignant disease diagnosis within the preceding 2 years with the exception of non- melanomatous skin cancer and carcinoma in situ |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Best response rate (CR+iCR+MLFS) at end of 4 cycles of treatment |
At 30 days
At 60 days
At 180 days and
Once in a year |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
MRD negative rate by flowcytometry (less than 0.01% with a sensitivity of 10-5)
Event free survival defined as relapse or death due to any cause from date of
enrolment in study
Overall survival defined as death due to any cause from date of enrolment in study |
At 30 days
At 60 days
At 180 days and
Once in a year |
|
|
Target Sample Size
|
Total Sample Size="183"
Sample Size from India="183"
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)
|
18/03/2024 |
| 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)
|
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
|
Introduction: Acute myeloid leukemia (AML) is a potentially curable hematological malignancy but remains one of the most challenging and expensive hematological malignancy to manage. In India these challenges are further exacerbated by high incidence of multi-drug resistant infections and a high out of pocket expense that results in a high induction mortality and limited access to therapy for most patients with a diagnosis of AML, using a conventional intensive chemotherapy that is offered for this disease in young adults (<60 years). There is a felt need to introduce and optimize de-intensified induction therapy with limited off- target side effects. Over the span of two India Alliance Senior Fellowships we have evaluated drug resistance in acute promyelocytic leukemia (APL), a subtype of AML, and in AML. We have also observed and reported on a unique metabolic vulnerability in AML that can be targeted effectively by re-purposing arsenic trioxide (ATO) and artesunate (ART), an anti-malarial drug. The pre-clinical work has been completed. The key goal of this project is to translate this potentially efficacious and low-cost intervention into standard treatment algorithms for AML through an academic clinical trial and to develop additional novel strategies to predict response to this therapy.
Once we have completed the Phase I study we will move to the Phase II multi-centre RCT to compare the proposed low cost de-intensified intervention with a currently accepted standard of care therapy. |