Study to determine safety, efficacy and tolerability of Venetoclax in combination with Fludarabine, Citarabine and Idarubicin to achieve the absence of disease in newly diagnosed Acute Myeloid Leukemia not classified as low risk that is there is an intermediate risk or high that the disease recurs
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 21.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2018-000392-33-IT
- Lead Sponsor
- FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 124
- Patients with newly diagnosed non-m3 acute myeloid leukemia documented / confirmed according to WHO 2017 diagnostic criteria
- The haematological pathology must be classified as intermediate or high risk according to the ELN criteria
- Patients between the ages of 18 and 65
- ECOG Performance Status = 2
- Patients with life expectancy> 12 weeks
- Patients may have Acute Myeloid Leukemia arising after previous treatment or other antecedent pathology
- 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
- 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 Investigator's judgment, the level of serum creatinine may not reflect renal function
- All non-haematological adverse events should be resolved to = 2 NCI-CTCAE, prior to initiation of therapy.
- Patients should be considered suitable by the Investigator to receive the chemotherapy combination.
- The chemotherapy combination should not be considered toxic without waiting for a benefit for the patient
- For women of child-bearing potential, a negative pregnancy test must be documented within 72 hours prior to the first study drug administration
- 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 post-menopausal (= 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.
- Ability to understand and availability to sign informed consent.
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 118
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
- Patients with low risk AML according ELN criteria
- Patients with current clinical evidence of CNS leukemia.
-Patients with myeloproliferative syndromes assessed by bone marrow biopsy
-AML supervening after antecedent myelodysplastic syndromes of more than 6 months duration
-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
- 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.
- 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.
- 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
- 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.
- 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.
- Patients with creatinine clearance <40ml/min (crokoft-grault calculation will
be consider reliable for patients <65 years and with no history of renal
diseases)
- Patients who must receive strong CYP3A4 inducers or moderate/strong
CYP3A4 inhibitors while on study except for antifungal prophylaxis.
- HIV-positive patients receiving combination anti-retroviral therapy.
- Patients who refuse to potentially receive blood products and/or have
a hypersensitivity to blood products.
- Patients with a history of active or chronic infectious hepatitis unless serology
demonstrates clearance of infection.
- Patients who have a history of liver cirrhosis by radiologic, clinical or
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Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method