NPM1-MUTATED AML NEWLY DIAGNOSED OR PREVIOUSLY TREATED WITH HYPOMETHYLATING 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: Actinomicina D, Dactinomicina, Cosmegen
Product Code: [L01DA01]
Pharmaceutical Form: Powder for sol
Sponsors
PROF.BRUNANGELO FALINI,DR.SSA MARIA PAOLA MARTELLI,UNIVERSITA' DI PERUGIA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of NPM1-mutated AML based on detection of NPM1 mutations at molecular analysis58 and/or demonstration of aberrant cytoplasmic expression of nucleophosmin at immunohistochemistry18. 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 serum pregnancy test 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. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception and intrauterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. 6. Signed informed consent. The consent must be obtained prior to performing any study-related procedure. 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Diagnosis of acute promyelocytic leukemia and all the other NPM1 negative 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. Pregnant (negative serum pregnancy test is required in women of child-bearing potential) or lactating women. Unwillingness to practice effective birth control 6. Inability to comply with other requirements of the protocol 7. 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 newly diagnosed or previously treated with hypometilating agents NPM1-mutated AML patients, measured as the rate of complete remissions. ;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 ;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);Timepoint(s) of evaluation of this end point: 8 weeks (2 treatment cycles) | — |
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 immunohistochemical response evaluated in the bone marrow biopsy by detection of aberrant cytoplasmic dislocation of nucleophosmin (NPM1). • Molecular response (MRD), as defined by 3-log reduction in NPM1 mutant transcripts copies assessed by quantitative RT-PCR on peripheral blood and bone marrow. • Rate of adverse events (AE) and severe adverse events (SAE) ;Timepoint(s) of evaluation of this end point: 36 months | — |
Countries
Italy
Contacts
Public ContactSez. Ematologia e Immunologia Clini
Dip. di Medicina
Outcome results
None listed