Acute Myeloid Leukemia with NPM1 mutation. 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) 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) MedDRA version: 21.1 Level: PT Classification code 10081513 Term: Acute myel
Conditions
Interventions
Trade Name: PEGINTRON - 100 MCG POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE IN CARTUCCE A DUE SCOMPARTI IN 4 PENNE PRERIEMPITE + 4 AGHI + 8 TAMPONI USO SOTTOCUTANEO
Product Name: Azacitidina
Product
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subject must be greater than or equal to 18 years of age 2. Subject must have received previous diagnosis of NPM1mut AML with or without concomitant FLT3-TKD or FLT3-ITD 3. At screening, subject must have confirmed NPM1 type A, B, or D mutant transcripts 4. Subject must be eligible for alloSCT, according to transplant center policy 5. Subject must have undergone at least two cycles of conventional anthracycline- and cytarabine based chemotherapy, achieving first CR (CR1) 6. Subject must be in morphological CR1 with bone marrow detectable minimal residual disease (MRD) positivity, defined as qRT-PCR NPM1 transcript = 0.01/100 ABL1 copies and confirmed in two consecutive determinations performed at 2 to 4 weeks’ distance: a. Molecular progression is defined in patients with molecular persistence at low copy number as an increase of MRD copy number = 1 log10 between 2 positive samples. b. Molecular relapse is defined in patients previously tested MRD negative as an increase in MRD copy number = 1 log10 between 2 positive samples 7. Subject must have a projected life expectancy of at least 12 weeks. 8. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status =65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: 1. Subject has acute promyelocytic leukemia (APL) 2. Subject has known active CNS involvement with AML 3. Subject has received previous treatment with venetoclax and/or hypomethylating agents 4. Subject has undergone alloSCT for AML 5. Subject has more than 5% of bone marrow blast cells at screening bone marrow aspirate 6. Subject is known to be positive for HIV 7. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal) b. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate. 8. Cardiac history of CHF requiring treatment or Ejection Fraction = 50% or chronic stable angina; 9. DLCO = 65% or FEV1 = 65%; 10. Creatinine clearance 2 a. Class 2 is i. defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity ii. results in fatigue, palpitations, dyspnea, or anginal pain 12. Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post-menopausal women must be amenorrhoic for at least 12 months to be considered of non-child bearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drugs. 13. Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to determine the efficacy of venetoclax and azacitidine in preventing morphological relapse in adult NPM1mut AML patients who experience molecular relapse/progression during chemotherapy treatment or subsequent follow-up monitoring.;Secondary Objective: - To evaluate the rate of MRD-negativity achieved with venetoclax-azacitidine - To evaluate the number of patients who proceed to allogeneic stem cell transplant (alloSCT) - To evaluate the number of patients who proceed to alloSCT in MRD-negativity - To evaluate Overall Survival (OS) - To evaluate Progression-Free Survival (PFS) - To evaluate Molecular Disease-Free Survival (MDFS) - To evaluate Molecular progression-free survival (MPFS) - To evaluate safety and toxicity of venetoclax-azacitidine in the experimental setting;Primary end point(s): Percentage of patients who do not experience overt relapse at 6 months or within stem cell transplant;Timepoint(s) of evaluation of this end point: At 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): MRD negativity rate at 3 and 6 months and at transplant • Percentage of patients undergoing alloSCT in CR • Percentage of patients undergoing alloSCT in MRD negativity • Disease Progression rate at 3, 6 and 12 months and at transplant • Molecular Disease Progression at 3, 6 and 12 months and at transplant • Overall Survival (OS), defined as the number of days between the first study drug administration and death from any cause or lost to follow up. • Progression-Free Survival (PFS), defined as the number of days between the first study drug administration and any event including disease progression or death. • Molecular Disease-Free Survival (MDFS), defined as the number of days between the data of response (MRD negativity) and molecular disease progression or death. • Molecular progression-free survival (MPFS), defined as the number of days between the first study drug administration and molecular disease progression or death. • Safety and toxicity of venetoclax-azacitidine in the experimental setting;Timepoint(s) of evaluation of this end point: At 3,6 and 12 months | — |
Countries
Italy
Contacts
Public ContactCentro Dati
Fondazione GIMEMA Franco Mandelli Onlus
Outcome results
None listed