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

NCT ID: NCT03455504

Last Updated: 2024-04-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-26
• Study Completion Date: 2025-01-31

Brief 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.

Detailed 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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

FLAI + V400 mg

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax add in combination with fludarabine, cyratabine and idarubicine

Cohort 2

FLAI + V600 mg

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax add in combination with fludarabine, cyratabine and idarubicine

Interventions

Venetoclax

Venetoclax add in combination with fludarabine, cyratabine and idarubicine

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giovanni Martinelli

Role: STUDY_CHAIR

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) Meldola

Fabio Ciceri

Role: STUDY_DIRECTOR

Istituto S. Raffaele, Milan

Locations

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

Florence, , 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

Milan, , Italy

Ospedale Niguarda "Ca Granda" SC Ematologia

Milan, , Italy

U.O. Ematologia e Trapianto di Midollo Ist. Scientifico Ospedale San Raffaele

Milan, , 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, , Italy

Countries

Italy

References

Marconi G, Piciocchi A, Audisio E, Papayannidis C, Cerrano M, Minotti C, Paoloni F, Guolo F, Bocchia M, Rondoni M, Lico A, Carrabba MG, Della Porta MG, Frigeni M, Giaccone L, Beltrami G, Cattaneo C, Di Chio MC, Serio B, Crea E, Freilone R, Capria S, Curti A, Minetto P, la Sala E, Nanni J, Zannetti BA, Simonetti G, Bochicchio MT, Saglio G, Lemoli RM, Venditti A, Vignetti M, Fazi P, Martinelli G. Safety run-in and part 1 of GIMEMA AML1718: venetoclax combined with FLAI as induction treatment in non-low-risk AML. Blood Adv. 2025 May 27;9(10):2542-2552. doi: 10.1182/bloodadvances.2024014901.

Reference Type: DERIVED

PMID: 40048742 (View on PubMed)

Related Links

http://www.gimema.it

GIMEMA Foundation

Other Identifiers

2018-000392-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AML1718

Identifier Type: -

Identifier Source: org_study_id