Status:
UNKNOWN
Venetoclax and Azacitidine for the Management of Molecular Relapse/Progression in Adult NPM1-mutated Acute Myeloid Leukemia
Lead Sponsor:
Gruppo Italiano Malattie EMatologiche dell'Adulto
Conditions:
Acute Myeloid Leukemia
Acute Myeloid Leukemia, in Relapse
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients...
Detailed Description
This is a phase 2, non-randomized, interventional, open-label, multicenter trial evaluating the efficacy of VEN-AZA as a bridge-to-transplant therapy in chemotherapy-treated adult NPM1mut AML patients...
Eligibility Criteria
Inclusion
- Subject must be ≥ 18 years of age
- Subject must have received previous diagnosis of NPM1mut AML with or without concomitant FLT3-TKD or FLT3-ITD
- At screening, subject must have confirmed NPM1 type A, B, or D mutant transcripts
- Subject must be eligible for alloSCT, according to transplant center policy
- Subject must have undergone at least two cycles of conventional anthracycline- and cytarabine-based chemotherapy, achieving first CR (CR1)
- 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
- 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.
- Molecular relapse is defined in patients previously tested MRD negative as an increase in MRD copy number ≥ 1 log10 between 2 positive samples
- Subject must have a projected life expectancy of at least 12 weeks.
- Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status \< 2
- Subject must have adequate renal and hepatic function per local laboratory reference range as follows:
- Aspartate transaminase (AST) and alanine transaminase (ALT) \< 3.0X ULN
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
- Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours' urine collection.
- Female subjects of childbearing potential must have negative results for pregnancy test at screening
- Female and male patients who are fertile must agree to use an effective form of contraception with their sexual partners from screening through 3 months after the end of treatment.
- Signed written informed consent according to ICH/EU/GCP and national local laws.
Exclusion
- Subject has acute promyelocytic leukemia (APL)
- Subject has known active CNS involvement with AML
- Subject has received previous treatment with venetoclax and/or hypomethylating agents
- Subject has undergone alloSCT for AML
- Subject has more than 5% of bone marrow blast cells at screening bone marrow aspirate
- Subject is known to be positive for HIV
- Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
- Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
- 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.
- Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina;
- DLCO ≤ 65% or FEV1 ≤ 65%;
- Creatinine clearance \< 30 ml/min
- Subject has a cardiovascular disability status of New York Heart Association Class \> 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
- 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.
- Patients unwilling or unable to comply with the protocol.
Key Trial Info
Start Date :
March 1 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
January 1 2025
Estimated Enrollment :
35 Patients enrolled
Trial Details
Trial ID
NCT04867928
Start Date
March 1 2022
End Date
January 1 2025
Last Update
March 16 2022
Active Locations (1)
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1
EMATOLOGIA- AOU Policlinico S.Orsola
Bologna, Italy