Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction for Acute Myelid Leukemia (V-FIRST)

Gruppo Italiano Malattie EMatologiche dell'Adulto

Status and phase

Active, not recruiting

Phase 2

Conditions

Acute Myeloid Leukemia

Treatments

Drug: Venetoclax

Study type

Interventional

Funder types

Other

Identifiers

NCT03455504

AML1718

2018-000392-33 (EudraCT Number)

Details and patient eligibility

About

This study will test the effectiveness and safety of Venetoclax in combination with standard induction regimen for patients with acute leukemia and poor prognosis.

Full description

Intensive treatment of Acute Leukemia, multidrug based chemotherapy induction, achieves complete remission (CR) rates ranging from 50% to 80%. Nonetheless, the majority (60- 70%) of responding patients will eventually relapse.

Patients with non-low risk leukemia according most diffuse risk scores have a poor prognosis and a short survival. For these patient traditional chemotherapy seems to be ineffective, even with BMT consolidation, probably due to activation of survival pathways in Leukemia cells, so that novel therapeutic interventions should be attempted.

This study will test the effectiveness and safety of Venetoclax, a selective BCL2 inhibitor, in combination with standard induction regimen.

Inhibiting anti-apoptotic pathway of BCL2, the investigators expect to improve success rate of standard chemotherapies.

Enrollment

124 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with documented/confirmed new onset non-m3 acute myeloid leukemia, according to WHO 2017 will be eligible for this study.
Hematological illness has to be graded intermediate or high risk according ELN criteria
Patients ≥ 18 years old and ≤ 65 years old
ECOG performance status ≤ 2.
Patients with a life expectancy >12 weeks
Patients may have AML which has arisen from prior therapies or other antecedent disorder
Adequate hepatic function
Adequate pancreatic function
Adequate renal function assessed by: Serum creatinine within reference laboratory ranges or creatinine clearance (by Cockcroft Gault formula, see Appendix 2) ≥ 50 mL/min for patients in whom, in the Investigator's judgment, serum creatinine level may not adequately reflect renal function.
All non-hematological adverse events must have resolved to NCI-CTCAE Grade ≤ 2 prior to starting therapy.
Patients must be considered by Investigator suitable to receive combination chemotherapy.
Combination chemotherapy has not to be considered toxic without expectation of any benefit for the patient
For females of childbearing potential, a negative pregnancy test must be documented within 72 hours prior to the first study drug administration.
All patients must be willing to use effective methods of contraception, during the treatment period and for 100 days after the last dose of Venetoclax. Female patients must be postmenopausal (≥ 1 year of amenorrhea), surgically sterile, or they must agree to use 2 adequate methods of contraception with at least one method with a failure rate of

≤ 1% per year (e.g., hormonal implants, combined oral contraceptives, vasectomized partner) and the second preferably a physical barrier method of contraception. Oral or injectable contraceptive agents cannot be the sole method of contraception. Male patients must be surgically sterile or agree to use an acceptable method of contraception.
Patient must be willing to submit the blood sampling and bone marrow sampling for the PK and PD analyses and exploratory biomarkers.
Ability to understand and willingness to sign an informed consent form.
Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion criteria

Patients with low risk AML according ELN criteria
Patients with current clinical evidence of CNS leukemia.
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
Patients who are on anti-microbial agents with therapeutic intent