| CTRI Number |
CTRI/2023/02/050069 [Registered on: 24/02/2023] Trial Registered Prospectively |
| Last Modified On: |
23/02/2023 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Phase 1b/2 Study of the drug venetoclax in combination with induction chemotherapy(ara-c and daunorubicin)in patients with newly diagnosed or relapsed/refractory AML. |
|
Scientific Title of Study
|
Venetoclax with chemotherapy for remission induction in AML patients a phase Ib/II study |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
sabitha P |
| Designation |
senior resident |
| Affiliation |
all india institute of New Delhi |
| Address |
First floor, DR.B.R.A. IRCH, Department of Medical Oncology, AIIMS, NEW DELHI
New Delhi
DELHI
110029
India |
| Phone |
9003003727 |
| Fax |
|
| Email |
sabithaparamasivam@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
sabitha P |
| Designation |
senior resident |
| Affiliation |
all india institute of New Delhi |
| Address |
First floor, DR.B.R.A. IRCH,
Dept of Medical Oncology,
AIIMS, New Delhi
New Delhi
DELHI
110029
India |
| Phone |
9003003727 |
| Fax |
|
| Email |
sabithaparamasivam@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
sabitha P |
| Designation |
senior resident |
| Affiliation |
all india institute of New Delhi |
| Address |
First floor, DR.B.R.A. IRCH,
Dept of medical oncology,
AIIMS, New Delhi
New Delhi
DELHI
110029
India |
| Phone |
9003003727 |
| Fax |
|
| Email |
sabithaparamasivam@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences, New Delhi |
|
|
Primary Sponsor
|
| Name |
All India Institute of Medical Sciences |
| Address |
IRCH,All India Institute of Medical Sciences, New Delhi 110029 |
| Type of Sponsor |
Research institution and hospital |
|
|
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 |
| Ranjit Kumar Sahoo |
DR.B.R.A. IRCH |
ROOM NO 218,FIRST FLOOR,IRCH, ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI,110029
New Delhi
DELHI |
9013956187
drranjitmd@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| DR.B.R.A.IRCH, AIIMS NEW DELHI |
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 |
| Intervention |
daunorubicin and cytarabine and venetoclax |
1. Daunorubicin intravenously over 30 min with doses 45 or 60 mg for 2 or 3 days
2. Cytarabine 100 mg/m2 subcutaneously over 3 to 5 min for 5 or 7 days
3. Venetoclax 400 mg per day or 100 mg along with Tab Voriconazole for total of 7 days
|
| Comparator Agent |
NIL |
NIL |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
1. Diagnosis of AML by WHO criteria
2. TLC less than or equal to twenty five thousand per cubic millimeter
3. Patients more than or equal to eighteen years
4. Eastern Cooperative Oncology Group (ECOG) performance status of zero to two
5. Newly diagnosed and relapsed (minimum of one prior line of AML directed therapy) to standard AML therapy will be eligible
6. Organ functions
a.Renal function with creatinine clearance more than thirty milli litre per minute based on Cockcroft – gault equation
b.Hepatic function including total bilirubin less than 1.5 times upper limit of normal unless increase is due to gilberts disease or leukemic involvement and AST and or ALT less than three times upper limit of normal unless considered due to leukemic involvement
|
|
| ExclusionCriteria |
| Details |
1. Infection with HIV or hepatitis B or C
2. Patients with NYHA class III or IV congestive heart failure
3. History of myocardial infection or unstable angina within last six months
4. Psychiatric illness that would adversely affect the participation in this study
5. Pregnant and lactating women
6. Baseline presentation with TLS
|
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| At the end of induction, to assess the rate of composite complete remission (CRc) including CR and CRi according to the modified International Working Group response criteria |
At the end of induction, at 28 days or at the time of count recovery, maximum to 42 days |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
1.Minimal residual disease by flow cytometry(MRD)
2.Adverse events(AEs)
3.Event free survival(EFS)
4.Overall survival(OS)
5.Induction mortality rates
|
1.MRD at the end of induction
2.adverse events through out the induction
3.EFS two years
4.OS two years
5.induction mortality rate at the end of induction |
|
|
Target Sample Size
|
Total Sample Size="97"
Sample Size from India="97"
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)
|
27/02/2023 |
| 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
|
nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
AML therapy has progressed far beyond the treatment regimen with ‘3 + 7’ intensive chemotherapy (3 days of anthracycline and 7 days of cytarabine). It is an alarm to improvise or define new standard chemotherapy regimen there by able to reduce the induction mortality which is in higher percentage particularly in LMIC.Despite high induction mortality, disease relapses are common and long-term outcomes remain poor. There comes venetoclax a potent, selective small molecule inhibitor of BCL-2 have activity against AML in R/R setting and in frontline combination therapy with hypomethylating agents, low dose cytarabine and other intense chemotherapy regimens. The ability of venetoclax to decrease the apoptotic threshold and the synergistic activity with the cytotoxic drugs make it an ideal drug to use as combination therapy in AML patients. Added to that, there is a deeper response and decrease in mortality as compared to the standard 3 + 7 chemotherapy regimen.
we planned this phase Ib/II study to define optimum chemotherapy dose and regimen with venetoclax in young and fit AML patients.In phase II study, we are stratifying furthur into relapsed AML and newly daignosed AML patients to assess the outcomes. |