Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction for Acute Myelid Leukemia

Acute Myeloid Leukemia Clinical Trial

— V-FIRST  

Official title:

Study Investigating Safety, Tolerability and Effectiveness of Venetoclax Add in Combination With Fludarabine, Cyratabine and Idarubicine in Induction of New Onset Non-M3 Acute Myelid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03455504
• Other study ID #: AML1718
• Secondary ID: 2018-000392-33
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 26, 2018
• Est. completion date: January 2025

Study information

• Verified date: April 2024
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Venetoclax
Venetoclax add in combination with fludarabine, cyratabine and idarubicine

Locations

Country	Name	City	State
Italy	Ematologia - ASST Papa Giovanni XXIII	Bergamo
Italy	Aou Di Bologna - Policlinico S. Orsola-Malpighi - Uoc Ematologia	Bologna
Italy	Spedali Civili - Azienda Ospedaliera U.O. Ematologia	Brescia
Italy	Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"	Catania
Italy	A.O.U. Careggi - Ematologia	Firenze
Italy	Irccs Aou San Martino - Genova - Uo Clinica Ematologica	Genova
Italy	Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori IRST	Meldola
Italy	Fondazione Irccs "Istituto Nazionale Tumori" - Milano - Sc Ematologia	Milano
Italy	Ospedale Niguarda "Ca Granda" SC Ematologia	Milano
Italy	U.O. Ematologia e Trapianto di Midollo Ist. Scientifico Ospedale San Raffaele	Milano
Italy	Asl Salerno, Presidio Ospedaliero Tortora Pagani - Ematologia	Pagani
Italy	U.O.C. Ematologia e CTMO Az Ospedaliero Universitaria	Parma
Italy	Fondazione Ircss Policlinico San Matteo - Pavia - Uo Ematologia	Pavia
Italy	Dipartimento Oncologico - Ospedale S. Maria delle Croci	Ravenna
Italy	Università degli Studi "Sapienza" Dip. Biotecnologie Cellulari ed Ematologia	Roma
Italy	Università Degli Studi Di Roma "Sapienza" - Dipartimento Di Medicina Traslazionale E Di Precisione - U.O.C. Ematologia	Roma
Italy	Ististuto Clinico Humanitas - Rozzano - Uo Oncologia Medica Ed Ematologia	Rozzano
Italy	Aou "San Giovanni Di Dio E Ruggi D'Aragona" - Salerno - Uoc Ematologia E Trapianti Di Cellule Staminali Emopoietiche	Salerno
Italy	Aou Senese - Uoc Ematologia E Trapianti	Siena
Italy	Aou Città Della Salute E Della Scienza, Ospedale S. Giovanni Battista Molinette - Torino - Sc Ematologia - Università Degli Studi Di Torino	Torino
Italy	Dipartimento di Oncologia ed Ematologia S.C. -Città della Scienza di Torino San Giovanni Battista	Torino
Italy	Aulss 8 Berica - Ospedale Di Vicenza - Uoc Ematologia	Vicenza

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients achieving complete response (CR) after course 1 or course 2 if course 2 is administered (CR + CRi + CRp)	Efficacy in new onset, non ELN Low risk AML (safety run-in, part1, and part2). Effectiveness of Venetoclax added in combination with chemotherapy in obtaining Complete remission in new onset, non ELN Low risk AML (safety run-in, part1, and part2).	At 24 months from study entry

External Links

•   GIMEMA Foundation