VENETOCLAX for Acute myeloid leukaemia|Acute myeloid leukaemia (newly diagnosed, non-M3)

Inclusion criteria

• {"criterion_text":"- Patients with newly diagnosed non-m3 acute myeloid leukemia documented / confirmed according to WHO 2017 diagnostic criteria"}
• {"criterion_text":"- Patients should be considered suitable by the Investigator to receive the chemotherapy combination."}
• {"criterion_text":"- The chemotherapy combination should not be considered toxic without waiting for a benefit for the patient"}
• {"criterion_text":"- For women of child-bearing potential, a negative pregnancy test must be documented within 72 hours prior to the first study drug administration"}
• {"criterion_text":"- All patients should be willing to use effective contraception during the treatment period and for the next 100 days after the last dose of Venetoclax. Women must be postmenopausal (= 1 year of amenorrhea), surgically sterile, or have to consent to the use of 2 contraceptive methods with at least one method with a failure rate = 1% per year (eg hormonal devices, contraceptives combined oral, partners with vasectomies) and as a second, preferably a contraceptive barrier method. Oral or injectable contraceptive instruments can not be used as the only method. Male patients must be surgically sterile to consent to use an acceptable method of contraception"}
• {"criterion_text":"- Ability to understand and availability to sign informed consent."}
• {"criterion_text":"- The subject must voluntarily sign and date informed consent, approved by an Independent Ethics Committee (IEC) / Institutional Review Board (IRB), prior to the start of any screening or study-specific procedure"}
• {"criterion_text":"- The haematological pathology must be classified as intermediate or high risk according to the ELN criteria"}
• {"criterion_text":"- Patients between the ages of 18 and 65"}
• {"criterion_text":"- ECOG Performance Status = 2"}
• {"criterion_text":"- Patients with life expectancy> 12 weeks"}
• {"criterion_text":"- Patients may have Acute Myeloid Leukemia arising after previous treatment or other antecedent pathology"}
• {"criterion_text":"- Adequate hepatic function as established by the following criteria: 1) Total serum bilirubin = 2 above the normal limit, if not considered for Gilbert's syndrome or a hepatic infiltration of leukemia 2) Alanine aminotransferase (ALT) =2.5 higher at the normal limit (or below the limit of normality of the reference laboratory, in the case of hepatic leukemia infiltration) 3) Aspartate aminotransferase (AST) =2.5 higher than the normal limit (or = 5 higher than the normal limit of the reference case, in case of hepatic infiltration of leukemia) 4) Adequate pancreatic function as established by the following criterion: serum lipase and amylase =2 higher than the normal limit"}
• {"criterion_text":"- Adequate renal function, principle based on: serum creatinine in the reference laboratory or creatinine clearance (based on the Cockcroft Gault formula) = 50 ml / min for patients in whom, according to the Inve"}
• {"criterion_text":"- All non-haematological adverse events should be resolved to = 2 NCI-CTCAE, prior to initiation of therapy."}

Exclusion criteria

• {"criterion_text":"- Patients with low risk AML according ELN criteria"}
• {"criterion_text":"- Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia (corrected for serum albumin level), hypomagnesemia, and hypomagnesemia of Grade = 2, as per NCICTCAE, version 5 which cannot be corrected prior to study initiation."}
• {"criterion_text":"- Patients with creatinine clearance <40ml/min (crokoft-grault calculation will be consider reliable for patients <65 years and with no history of renal diseases)"}
• {"criterion_text":"- Patients who must receive strong CYP3A4 inducers or moderate/strong CYP3A4 inhibitors while on study except for antifungal prophylaxis."}
• {"criterion_text":"- HIV-positive patients receiving combination anti-retroviral therapy."}
• {"criterion_text":"- Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products."}
• {"criterion_text":"- Patients with a history of active or chronic infectious hepatitis unless serology demonstrates clearance of infection."}
• {"criterion_text":"- Patients who have a history of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests."}
• {"criterion_text":"- Patients who have had prior BCL-2 antagonists."}
• {"criterion_text":"- Pregnant or breast feeding patients."}
• {"criterion_text":"- Patients with reproductive potential not willing to use effective methods of contraception."}
• {"criterion_text":"- Patients with current clinical evidence of CNS leukemia."}
• {"criterion_text":"- Patients with myeloproliferative syndromes assessed by bone marrow biopsy"}
• {"criterion_text":"- AML supervening after antecedent myelodysplastic syndromes of more than 6 months duration"}
• {"criterion_text":"- Any patient with an history of neoplastic disease with the exception of: a. patients with non-melanoma skin cancer or stage I cancer who do not received systemic chemotherapy or radiation whom cancer where completely removed from at least 1 year a.b. patients who are alive, in complete remission and with no evidence of the neoplasia from at least 5 years"}
• {"criterion_text":"- Patients receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy with the exception of Hydroxyurea (HU) or 6-Mercaptopurine (6MP) in patients who need to continue this agent to maintain WBC count =10,000/mm3. HU and 6MP must be discontinued at the time of initiation of study medications."}
• {"criterion_text":"- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study including but not limited at: unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication (does not include stable, lone atrial fibrillation), QTcF = 480 msecs based on the average of 3 screening ECG’s, uncontrolled hypertension, symptomatic congestive heart failure (NYHA III, IV), ejection fraction <40, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study treatment start, any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study."}
• {"criterion_text":"- Patients who are on anti-microbial agents with therapeutic intent for the following conditions: Fungal infection with visceral involvement, other than mucosal candidiasis, with = 2 weeks of appropriate systemic antifungal therapy, Bacterial infection with positive blood cultures in the 7 days prior to dosing or with= 5 days of appropriate therapeutic antibiotic therapy, Neutropenic fever considered infection-related within 72h prior to dosing, Infection considered by the investigator to be clinically uncontrolled or at unacceptable risk to the patient upon induction of neutropenia"}
• {"criterion_text":"- Patients with nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by this study treatment, such as, severe diabetes mellitus that is not controlled with medical management."}

Primary endpoints

• {"endpoint_text":"- Primary end point is % of CR (CR + CRi + CRp) after course 1 or course 2 if course 2 is administered","definition_or_measurement_approach":"Percentage of patients achieving Complete Remission (CR + CRi + CRp) measured after course 1 or after course 2 if course 2 is administered."}

Secondary endpoints

• {"endpoint_text":"- Incidence time and nature of any adverse event.","definition_or_measurement_approach":"Incidence, timing and characterization (nature) of adverse events collected throughout study treatment and follow-up."}
• {"endpoint_text":"- Severe effect related to treatment safety is defined as an adverse event occurring within the first cycle, judged to be related to treatment and meeting any of the following criteria: 1) Grade 3 non- hematological toxicity lasting more than 7 days 2) Grade 4 non- hematological toxicity.","definition_or_measurement_approach":"Treatment-related adverse events within first cycle meeting specified CTCAE grade and duration criteria (Grade 3 non-hematological toxicity >7 days; Grade 4 non-hematological toxicity)."}
• {"endpoint_text":"- DLT as any grade 4 non-infective and non-hematologic adverse event that for the experience of the investigator cannot be due to FLAI chemotherapy alone and any grade 5 adverse event","definition_or_measurement_approach":"Dose-limiting toxicity (DLT) defined as grade 4 non-infective non-hematologic AE not attributable to FLAI alone, or any grade 5 AE."}
• {"endpoint_text":"- Incidence, severity, seriousness and treatment-causality of Treatment Emergent Signs and Symptoms.","definition_or_measurement_approach":"Assessment of treatment-emergent signs/symptoms including incidence, severity, seriousness and investigator-assessed causality."}
• {"endpoint_text":"- Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, vital signs and 12-Lead ECG","definition_or_measurement_approach":"Monitoring and reporting of clinically significant abnormalities in physical exam, safety labs, vitals and 12-lead ECGs."}
• {"endpoint_text":"- TLS occurred during or after protocol or transplant procedures for up to 1 years.","definition_or_measurement_approach":"Recording incidence of tumor lysis syndrome (TLS) occurring during or after protocol or transplant procedures, monitored for up to 1 year."}
• {"endpoint_text":"- Description of patient-reported QoL over time","definition_or_measurement_approach":"Patient-reported quality of life measured over time using specified QoL instruments (details not provided in the available record)."}

Italy

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

05-08-2024

Processing Time Days

25

Number Of Sites

22

Number Of Participants

124

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":"IRCCS Ospedale Policlinico San Martino","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Italy","full_name":"Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}