Study the effects of azacitidine and lenalidomide combination therapy in patients with acute myeloid leukemia

Phase 1

• Conditions: ACUTE MYELOID LEUKEMIA; MedDRA version: 21.0Level: LLTClassification code 10024289Term: Leukaemia acuteSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-001767-40-IT
• Lead Sponsor: AZIENDA OSPEDALIERA OSPEDALI RIUNITI MARCHE NORD

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-10
• Last Update Posted: 9 January 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

•Diagnosis of relapsed AML. A prior CR duration of at least 2 months is required to met the definition of relapsed AML. Patients must have not received more than 1 re-induction course prior to enter the study.
•Diagnosis of resistant AML. Patients must have received, at the upmost, 2 courses of therapy (first induction and first salvage course) before entering the study, in order to be eligible for enrolment.
•Patients relapsing after stem cell transplantation, both autologous and allogeneic, are eligible.
•HIV negativity.
•Male and female patients aged = 60 and = 70 years.
•Signed informed consent
•Morphologically confirmed diagnosis of non-M3 acute myeloid leukemia (AML) in first or subsequent relapse by bone marrow aspiration
•WBC count = 30,000/mm³. A pretreatment with single dose vinblastine in order to reduce the white blood cell count is allowed within 7 days from the start of therapy. Cytoreduction with hydroxyurea is not allowed.
•Patient must be not eligible for or not interested in conventional salvage therapies.
•Fertile male patients must use a condom during sexual contact with a pregnant female or a FCBP while taking lenalidomide, during dose interruptions and for at least 28 days after the last dose of lenalidomide, even if he has undergone a successful vasectomy.
•Female patients must be in menopause (natural menopause for at least 24 consecutive months, a hysterectomy, or bilateral oophorectomy) to enter the study
•Karnofsky score > 60% at study entry
•Patients fitness will be evaluated according to the SIE, SIES and GITMO Guidelines (Ferrara et al, Leukemia 2013)
•Adequate renal, pulmonary and hepatic function, intended as follows:
o Bilirubin = 2.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction)
o AST and ALT = 3.5 times ULN
o Creatinine = 2 times ULN

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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 51

Exclusion Criteria

• Acute promyelocytic leukemia (FAB M3)
• Cytoreduction with hydroxyurea
• Male and female patients aged <60 years and >70 years
• Patients with resistant AML who have received more than 2 courses or more of reinduction chemotherapy
• Blastic transformation of chronic myeloid leukemia
• Absence of patient’s written informed consent
• Active opportunistic infections
• HIV infection
• Active second malignancy
• Intercurrent organ damage or medical problems that would interfere with therapy
• Concurrent therapy for another malignancy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Determine the efficacy of combined azacitidine and lenalidomide for non-M3 acute myeloid leukemia (AML) patients aged = 60 and =70 years.;Secondary Objective: Determine the frequency and severity of toxic effects of this regimen in these patients.To define cellular factors associated with clinical response to combined azacitidine and lenalidomide and determine the mechanisms underlying the synergistic effect between azacitidine and lenalidomide on ex vivo model and GEP analysis.<br>To investigate the survival parameters of patients on this study;Primary end point(s): To assess the complete remission (CR) rate, including CRi;Timepoint(s) of evaluation of this end point: Start: march 2016<br><br>End Accrual Phase II: september 2017<br><br>Final Study Report: december 2019 <br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess overall survival.To assess event-free survival. To assess safety of the combination regimen, considered as the incidence of adverse event (graded according to WHO) and clinically significant abnormal laboratory values following chemotherapy. To assess the relationship of cytogenetic and molecular findings with response to treatment;Timepoint(s) of evaluation of this end point: Start: march 2016<br><br>End Accrual Phase II: september 2017<br><br>Final Study Report: december 2019 <br>