patients with NPM1-wild type AML (other than APL) aged >= 70 years old and/or unfit for intensive chemotherapy, either newly diagnosed or previously treated with hypometylating agents MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: COSMEGEN - 0.5 MG POLVERE PER SOLUZIONE INIETTABILE 1 FLACONCINO DA 0.5 MG
Product Name: Dactinomicina, Actinomicina D, Cosmegen
Product Code: [L01DA01 - Dactinomicina]
Pharmaceutical Form
Sponsors
PROF.BRUNANGELO FALINI,DR.SSA MARIA PAOLA MARTELLI,UNIVERSITA' DI PERUGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria In order to be enrolled into the study, patients must fulfil the following criteria: 1. Diagnosis of AML with NPM1-wild type genotype (lack of NPM1 mutations as detected at molecular analysis35 and/or at immunohistochemistry24). 2. Age =70 years, or age 18-70 years and being unsuitable for intensive chemotherapy. Ineligibility for intensive chemotherapy will be based on investigator assessment of patient characteristics such as age, performance status, concomitant co-morbidities and organ dysfunction (Döhner H et al., Blood 2014 Aug 28;124:1426-33). 3. Adequate renal and liver function as defined by the following laboratory values performed within 7 days prior to first dose of actinomycin D: serum creatinine =2.0 mg/dl; serum aspartate transaminase (AST) and serum alanine transaminase (ALT) =3 times the upper limit of normal (ULN), alkaline phosphatase =2.5 times ULN and bilirubin =1.5 times the ULN. Higher values are acceptable if they are directly related to the disease. 4. Negative pregnancy test (serum or urinary HCG) within 7 days prior to commencement of treatment in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for =1 year 5. Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as indicated by their physician. Highly effective contraception methods include: - Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. - Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male sterilization. - Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Exclusion Criteria A patient will be excluded if the answer to any of the following statements is "yes": 1. Diagnosis of acute promyelocytic leukemia or NPM1-mutated AML. 2. Central nervous system (CNS) leukemia involvement because actinomycin D does not cross the blood-brain barrier. 3. Concurrent administration of any anti-leukemic therapy (e.g. chemotherapy, experimental drug, etc.) other than actinomycin D. 4. Known hypersensitivity to actinomycin D 5. Active infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator. 6. Pregnant (negative serum pregnancy test is required in women of child-bearing potential) or lactating women. Unwillingness to practice effective birth control 7. Inability to comply with other requirements of the protocol 8. Unwillingness to participate to the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the clinical efficacy of single agent actinomycin D administered intravenously in NPM1-wild type AML patients ;Secondary Objective: • To assess the safety of actinomycin D • To determine the duration of response to actinomycin D • To assess time to neutrophil (PMN>1000/¿l) and platelet (PLT>50000/¿l) recovery either after the first cycle or after each subsequent cycle • To assess the need for transfusional support (platelets and blood red cells) during the first induction cycle and the subsequent cycles • To assess the molecular response ;Primary end point(s): The complete hematological response rate after two cycles of treatment. The complete hematological response rate is intended as the sum of complete response (CR) and complete response with incomplete marrow recovery (CRi), defined according to the criteria indicated below. ;Timepoint(s) of evaluation of this end point: 2 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The overall survival (OS) • The disease free survival (DFS) as defined by relapse and death in remission. • Cumulative incidence of relapse • The molecular response as assessed by quantitative RT-PCR for WT1 copies on peripheral blood. • Rate of adverse events (AE) and severe adverse events (SAE) as defined below. ;Timepoint(s) of evaluation of this end point: 18 months | — |
Countries
Italy
Contacts
Public ContactSez. di Ematologia
Dip. di Medicina
Outcome results
None listed