VENETOCLAX for Acute myeloid leukemia (NPM1-mutated)

Inclusion criteria

• {"criterion_text":"- Subject must be greater than or equal to 18 years of age"}
• {"criterion_text":"- Female subjects of childbearing potential must have negative results for pregnancy test at screening"}
• {"criterion_text":"- Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from screening through 3 months after the end of treatment."}
• {"criterion_text":"- Signed written informed consent according to ICH/EU/GCP and national local laws."}
• {"criterion_text":"- Subject must have received previous diagnosis of NPM1mut AML with or without concomitant FLT3-TKD or FLT3-ITD"}
• {"criterion_text":"- At screening, subject must have confirmed NPM1 type A, B, or D mutant transcripts"}
• {"criterion_text":"- Subject must be eligible for alloSCT, according to transplant center policy"}
• {"criterion_text":"- Subject must have undergone at least two cycles of conventional anthracycline- and cytarabine based chemotherapy, achieving first CR (CR1)"}
• {"criterion_text":"- Subject must be in morphological CR1 with bone marrow detectable minimal residual disease (MRD) positivity, defined as qRT-PCR NPM1 transcript = 0.01/100 ABL1 copies and confirmed in two consecutive determinations performed at 2 to 4 weeks’ distance: a. Molecular progression is defined in patients with molecular persistence at low copy number as an increase of MRD copy number = 1 log10 between 2 positive samples. b. Molecular relapse is defined in patients previously tested MRD negative as an increase in MRD copy number = 1 log10 between 2 positive samples"}
• {"criterion_text":"- Subject must have a projected life expectancy of at least 12 weeks."}
• {"criterion_text":"- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status < 2"}
• {"criterion_text":"- Subject must have adequate renal and hepatic function per local laboratory reference range as follows: - Aspartate transaminase (AST) and alanine transaminase (ALT) < 3.0X ULN - Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of nonhepatic origin) - Subject must have adequate renal function as demonstrated by a creatinine clearance = 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours’urine collection."}

Exclusion criteria

• {"criterion_text":"- Subject has acute promyelocytic leukemia (APL)"}
• {"criterion_text":"- Creatinine clearance < 30 ml/min"}
• {"criterion_text":"- Subject has a cardiovascular disability status of New York Heart Association Class > 2 a. Class 2 is i. defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity ii. results in fatigue, palpitations, dyspnea, or anginal pain"}
• {"criterion_text":"- Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post-menopausal women must be amenorrhoic for at least 12 months to be considered of non-child bearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs."}
• {"criterion_text":"- Patients unwilling or unable to comply with the protocol"}
• {"criterion_text":"- Subject has known active CNS involvement with AML"}
• {"criterion_text":"- Subject has received previous treatment with venetoclax and/or hypomethylating agents"}
• {"criterion_text":"- Subject has undergone alloSCT for AML"}
• {"criterion_text":"- Subject has more than 5% of bone marrow blast cells at screening bone marrow aspirate"}
• {"criterion_text":"- Subject is known to be positive for HIV"}
• {"criterion_text":"- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) b. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate."}
• {"criterion_text":"- Cardiac history of CHF requiring treatment or Ejection Fraction = 50% or chronic stable angina;"}
• {"criterion_text":"- DLCO = 65% or FEV1 = 65%;"}

Primary endpoints

• {"endpoint_text":"- Percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- MRD negativity rate at 3 and 6 months and at transplant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Percentage of patients undergoing alloSCT in CR","definition_or_measurement_approach":""}
• {"endpoint_text":"- Percentage of patients undergoing alloSCT in MRD negativity","definition_or_measurement_approach":""}
• {"endpoint_text":"- Disease Progression rate at 3, 6 and 12 months and at transplant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Molecular Disease Progression at 3, 6 and 12 months and at transplant","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall Survival (OS), defined as the number of days between the first study drug administration and death from any cause or lost to follow up.","definition_or_measurement_approach":"Defined as the number of days between the first study drug administration and death from any cause or lost to follow up."}
• {"endpoint_text":"- Progression-Free Survival (PFS), defined as the number of days between the first study drug administration and any event including disease progression or death.","definition_or_measurement_approach":"Defined as the number of days between the first study drug administration and any event including disease progression or death."}
• {"endpoint_text":"- Molecular Disease-Free Survival (MDFS), defined as the number of days between the data of response (MRD negativity) and molecular disease progression or death.","definition_or_measurement_approach":"Defined as the number of days between the date of response (MRD negativity) and molecular disease progression or death."}
• {"endpoint_text":"- Molecular progression-free survival (MPFS), defined as the number of days between the first study drug administration and molecular disease progression or death.","definition_or_measurement_approach":"Defined as the number of days between the first study drug administration and molecular disease progression or death."}
• {"endpoint_text":"- Safety and toxicity of venetoclax-azacitidine in the experimental setting","definition_or_measurement_approach":""}

Italy

Earliest CTIS Part Ii Submission Date

12-06-2024

Latest Decision Or Authorization Date

19-01-2026

Processing Time Days

586

Number Of Sites

29

Number Of Participants

35

Primary sponsor

Full Name

Fondazione Gimema Franco Mandelli Onlus

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Laboratorio Centro Clinico Unità Operativa di Ematologia","duties_or_roles":"sponsorDuties code 4","organisation_type":"Health care"}
• {"country":"Italy","full_name":"Laboratorio di Diagnostica Integrata Oncoematologica “OPPO”","duties_or_roles":"sponsorDuties code 4","organisation_type":"Health care"}