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.

Phase 1/2

Not yet recruiting

Brief Summary: AML therapy has progressed far beyond the treatment regimen with â€˜3 + 7â€™ 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.

Recruitment & Eligibility

Inclusion Criteria

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 â€“ 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.

Exclusion Criteria

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.

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
1.Minimal residual disease by flow cytometry(MRD)	2.Adverse events(AEs)

Locations (1): DR.B.R.A. IRCH
🇮🇳
Delhi, DELHI, India
DR.B.R.A. IRCH
🇮🇳Delhi, DELHI, India
Ranjit Kumar Sahoo
Principal investigator
9013956187
drranjitmd@gmail.com