Preemptive treatment with venetoclax plus azacitidine in patients diagnosed with acute myeloid leukemia (AML) with persistence or reappearance of measurable residual disease (MRD) after frontline chemotherapy and high-level MRD prior to allogeneic hematopoietic cell transplantation (alloHCT)
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 29
A patient will be eligible for study participation if he/she meets the following criteria within 30 days prior to the first day of therapy (bone marrow biopsy can be performed 30 days prior to the first day of therapy). Historical records are permitted per investigator discretion., 9. Patients must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed screening procedures., 1. Patients must have confirmation of with acute myeloid leukemia (AML) with persistent measurable residual disease (MRD) or MRD reappearance after frontline intensive chemotherapy (including at least one cycle of cytarabine and anthracycline), and prior to allogeneic hematopoietic cell transplantation (allo-HCT). a. In patients with NPM1 mutation, qRT-PCR of NPM1 will be the method used to establish a molecular failure, defined as failure to achieve molecular response after consolidation therapy (NPM1mut/ABL1·100 > 0.01) or MRD reappearance after molecular response. All cases of molecular failure must be confirmed with a second MRD assessment in 2 to 4 weeks. b. In patients with core-binding factor AML, qRT-BCR of RUNX1-RUNX1T1 and CBFb-MYH11 transcripts will be used. Patients failing to achieve a major MRD reduction after consolidation therapy (i.e., RUNX1-RUNX1T1/ABL1·100>0.1 or CBFb-MYH11/ABL1·100>0.1), a log increase in MRD between two positive samples or confirmed MRD CETLAM-LMA-AC-2024-01- Protocol Version - 1.0 17JUL2023 Page 14/103 VERDI reappearance after molecular response will be considered as molecular failures and could be included in the trial. c. In the remaining cases, an appropriate leukemia-associated immunophenotype (LAIP) measured by multiparameter flow cytometry will be used for MRD surveillance. A cutoff of 0.1% will be used to define MRD positivity., 2. Age =18 years., 3. Without clinical signs of active central nervous system disease., 4. Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance status of =2 or Karnosky performance status (KPS) equivalent (Appendix, 5. Patients must have adequate renal function as demonstrated by a calculated creatinine clearance = 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula., 6. Patients must have adequate liver function as demonstrated by: a. aspartate aminotransferase (AST) = 3.0 × upper limit normal (ULN) b. alanine aminotransferase (ALT) = 3.0 × ULN c. bilirubin = 1.5 × ULN, unless due to Gilbert's syndrome, 7. Non-sterile male patients must use contraceptive methods with partner(s) prior to beginning study drug administration and continuing up to 3 months after the last dose of study drug. Male patients must agree to refrain from sperm donation from initial study drug administration until 3 months after the last dose of study drug., 8. WOCBP (Appendix 7) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting therapy; 2) throughout the entire duration of treatment; 3) during dose interruptions; and 4) for at least 6 months after discontinuation of therapy (last dose of study drug).
1. Patient has received other prior rescue treatment for MRD., 10. El paciente tiene antecedentes de otras neoplasias malignas durante el año anterior al ingreso al estudio, excepto: a. Carcinoma in situ de mama o cuello uterino adecuadamente tratado. b. Carcinoma de células basales de piel o carcinoma de células escamosas localizado de piel. c. Cáncer de próstata sin planes de terapia de ningún tipo. d. Neoplasia maligna previa confinada y resecada quirúrgicamente (o tratada con otras modalidades) con intención curativa., 11. Pregnant and breastfeeding females., 2. Patient is known to be positive for Human immunodeficiency virus (HIV). Note: HIV testing is not required., 3. Patient is known to be positive for hepatitis B (HBV) or C (HCV) infection with the exception of those with an undetectable viral load. CETLAM-LMA-AC-2024-01- Protocol Version - 1.0 17JUL2023 Page 15/103 VERDI Note: Hepatitis B or C testing is not required and patients with serologic evidence of prior vaccination to HBV (i.e., HBsAg-, anti-HBs+ and anti-HBc-) may participate., 4. El paciente tiene afectación activa conocida del sistema nervioso central (SNC) por leucemia mieloide aguda., 5. Patient has received within 7 days prior to the first dose of study drug: steroid therapy = 20 mg/day (prednisone or equivalent) for antineoplastic intent; strong and moderate CYP3A inhibitors; strong and moderate CYP3A inducers., 6. Patient has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment., 7. Patient has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to: a. New York Heart Association heart failure > class 2. b. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia., 8. Patient has a malabsorption syndrome or other condition that precludes the enteral route of administration., 9. Patient exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method