| CTRI Number |
CTRI/2025/12/098296 [Registered on: 02/12/2025] Trial Registered Prospectively |
| Last Modified On: |
01/12/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Assessing the effectiveness and safety of Venetoclax (a type of targeted therapy medicine) combination therapy in children with Acute Myeloid Leukemia (a common type of blood cancer). |
|
Scientific Title of Study
|
Evaluation of Venetoclax-Based Combination Therapies in Childhood Acute Myeloid
Leukemia: A Phase II Randomized Controlled Trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Shyam Srinivasan |
| Designation |
Associate Professor, Medical Oncology (Pediatrics) |
| Affiliation |
Tata Memorial Hospital |
| Address |
Department of Medical Oncology (Pediatric), Tata Memorial Hospital, HBB-1113, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Road, Parel, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9619983999 |
| Fax |
|
| Email |
srinivas.shyam@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Shyam Srinivasan |
| Designation |
Associate Professor, Medical Oncology (Pediatrics) |
| Affiliation |
Tata Memorial Hospital |
| Address |
Department of Medical Oncology (Pediatric), Tata Memorial Hospital, HBB-1113, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Road, Parel, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9619983999 |
| Fax |
|
| Email |
srinivas.shyam@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Shyam Srinivasan |
| Designation |
Associate Professor, Medical Oncology (Pediatrics) |
| Affiliation |
Tata Memorial Hospital |
| Address |
Department of Medical Oncology (Pediatric), Tata Memorial Hospital, HBB-1113, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Road, Parel, Mumbai
Mumbai
MAHARASHTRA
400012
India |
| Phone |
9619983999 |
| Fax |
|
| Email |
srinivas.shyam@gmail.com |
|
|
Source of Monetary or Material Support
|
| Lady Tata Memorial Trust, Bombay House 24, Homi Mody Street Mumbai - 400 001 Maharashtra, INDIA |
| Tata Memorial Centre Research Administration Council (TRAC),
Tata Memorial Hospital, 3rd Floor, Main Building, Dr. Ernest Borges Road, Parel, Mumbai-400012. Maharashtra. India |
|
|
Primary Sponsor
|
| Name |
Dr Shyam Srinivasan |
| Address |
Department of Medical Oncology (Pediatric), HBB-1113, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Road, Parel, Mumbai |
| Type of Sponsor |
Other [(Self-Intramural)] |
|
|
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 Shyam Srinivasan |
Tata Memorial Hospital |
Department of Medical Oncology (Pediatric), Tata Memorial Hospital, HBB-1113, 11th Floor, Homi Bhabha Block, Dr. Ernest Borges Road, Parel, Mumbai, MAHARASHTRA
Mumbai
MAHARASHTRA |
9619983999
srinivas.shyam@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C920||Acute myeloblastic leukemia, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Azacitidine |
Azacitidine is a chemotherapy drug classified as a demethylation agent and antimetabolite, primarily used to treat certain types of blood cancers, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
Duration: 7 days per cycle (Days 1–7).
Schedule: Administered once daily (QD) |
| Comparator Agent |
Cytarabine |
Cytarabine is a potent chemotherapy medication used primarily to treat various types of leukemia and lymphoma. It is an antimetabolite that works by interfering with cancer cell DNA synthesis and repair, thus blocking cell division. Duration: 5 days per cycle (Days 1–5). Schedule: Administered every 12 hours (q12h).After completing these 2 cycles, patients proceed to standard intensive chemotherapy (e.g., "3+7" protocol) |
| Intervention |
Venetoclax |
Venetoclax is a B-cell lymphoma-2 (BCL-2) inhibitor, which is a type of targeted cancer therapy.
Duration: 14 days per cycle (Days 1–14)
Schedule:
Administered once daily
Ramp-up (Cycle 1 only):
Day 1: 50 mg/m^2
Day 2: 100 mg/m^2
Day 3–14: 200 mg/m^2(target dose)
Subsequent Cycles: No ramp-up is required; dosing starts at 200 mg/m^2 from Day 15 |
|
|
Inclusion Criteria
|
| Age From |
1.00 Year(s) |
| Age To |
15.00 Year(s) |
| Gender |
Both |
| Details |
1.Subject must have histological confirmation of AML by WHO criteria, with greater than 5 percentage bone marrow blasts.
2.Subject must have adequate renal function as demonstrated by a creatinine clearance greater than and equal to 30 mL/min, calculated by the Cockcroft Gault formula or measured by 24-hours urine collection.
3.Subject must have adequate liver function as demonstrated by: aspartate aminotransferase (AST) less than and equal to 5.0 × ULN and alanine aminotransferase (ALT) less than and equal to 5.0 × ULN and bilirubin less than and equal to 3 × ULN
(Unless considered to be due to Leukemic organ involvement).
|
|
| ExclusionCriteria |
| Details |
1.Age less than 1 year or greater than 15 years.
2.Previous chemotherapy for AML, except for cytoreductive therapy (hydroxyurea or low dose cytarabine for up to 96 hours).
3.Relapsed or refractory AML
4.Secondary AML
5.Subject has known CNS involvement with AML
6.Diagnosis of myelodysplastic neoplasm
7.Diagnosis of acute promyelocytic leukemia (APL, AML-M3)
8.Core-binding factor AML
9.Acute megakaryocytic leukemia
10.Children with Down syndrome
11.Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
12.Subject has a white blood cell count greater than 25 × 10 to the power of 9 /L. (Note: Hydroxyurea or low-dose cytarabine for up to 96 hours administration or leukapheresis is permitted to meet this criterion).
13.Documented hypersensitivity to any component of the chemotherapy regimen.
|
|
|
Method of Generating Random Sequence
|
Stratified randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
To estimate if two different venetoclax based combination therapies can improve composite complete remission (CR + CRi) rates in treatment naïve childhood AML.
|
Baseline: Cycle 1 Day 1 (Pre-treatment).
4 Weeks: End of Cycle 1 (Day 28); first marrow evaluation.
8 Weeks: End of Cycle 2 (Day 56); Primary Endpoint analysis for composite complete remission (CR+CRi) |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| To determine efficacy of venetoclax based combination regimens based on genomic subgroups |
At the end of two cycles of venetoclax-based combination therapy.
|
To evaluate if venetoclax based combination improves the minimal residual disease (MRD) response
rate. |
MRD assessment at the end of cycles 1 and 2. |
To evaluate the apoptotic priming and mitochondrial dependence of leukemic blasts in children with
AML using BH3 profiling. |
Samples collected at baseline and end of cycle 1 for non-responders. |
To assess the toxicity profile of venetoclax-based therapies.
|
Continuous monitoring throughout the treatment period and for 30 days posttreatment. |
To assess the 2-year event-free survival (EFS) and overall survival (OS)
|
At 1 and 2 year from completion of intervention. |
|
|
Target Sample Size
|
Total Sample Size="74"
Sample Size from India="74"
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)
|
15/12/2025 |
| 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="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
|
Acute Myeloid Leukemia (AML) is a serious type of blood cancer that affects children.
Treating this disease requires strong chemotherapy, which can lead to side effects and even
death during treatment, especially in the early phase. We need better treatments that are
both effective and safer for children.
This study will test whether adding a new medicine called venetoclax, in combination with
other chemotherapy drugs, can be safely used in the early part of treatment. Venetoclax has
shown promise in adult patients and in smaller studies of children, but it has not yet been
widely tested in large groups of children with newly diagnosed AML.
In this study, we will give venetoclax along with two chemotherapy drugs (either cytarabine
or azacitidine) for the first 1–2 weeks of treatment. The main goal is to see if this new
approach helps children go into remission while keeping side effects manageable. We will
also closely monitor for any early complications like infections or low blood counts.
Apart from treatment, we will also study the biology of the disease in Indian children using
advanced laboratory techniques such as BH3 profiling, to understand how leukemia cells
respond to venetoclax. These tests will help us understand which children are most likely to
benefit from venetoclax and improve future treatment plans.
If the results of this study are promising, we plan to take this research further into larger
trials that could eventually change the way we treat childhood AML in India and similar
settings. We hope this study will lead to better outcomes with fewer side effects for children
with this serious illness. |