CHIP-AML22 Master protocol: An open label complex clinical trial in newly diagnosed pediatric de novo AML patients a study by the NOPHO-DB-SHIP consortium Master Protocol
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Leucemia linfática crónica y otros SLPC, Leucemia mieloide aguda, Trasplante de progenitores hematopoyéticos, Linfoma, Leucemia
CENTRO INVESTIGADOR
H.G.U. Gregorio Marañón
INVESTIGADOR PRINCIPAL
Marina García Morin
CENTRO INVESTIGADOR
H.U. La Paz
INVESTIGADOR PRINCIPAL
Berta González
FECHA DE APERTURA
Julio, 2024
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Newly diagnosed AML. The origin of AML must be de novo (not secondary to bone marrow failure or therapy-related).
Age 1 day and 18 years old at initial diagnosis.
Written informed consent/assent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations.
Able to comply with scheduled follow-up and with management of toxicity.
Additional inclusion criteria for the induction randomization: 1) CD33 positivity of leukemic blasts as measured by flow cytometry (mean fluorescence intensity; MFI) at diagnosis (bone marrow aspirate and/or peripheral blood). CD33 positivity is defined as a ratio of at least 10 (using the anti-CD33 clone P67.6) of the geometric MFI of CD33 for the blast population divided by the MFI of the CD33 background signal of lymphocytes. 2) Informed consent for participation in randomization Ri.
Additional inclusion criteria for the consolidation randomization 1) Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol. 2) Informed consent for participation in randomization Rc.
Age 1 day and 18 years old at initial diagnosis.
Written informed consent/assent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations.
Able to comply with scheduled follow-up and with management of toxicity.
Additional inclusion criteria for the induction randomization: 1) CD33 positivity of leukemic blasts as measured by flow cytometry (mean fluorescence intensity; MFI) at diagnosis (bone marrow aspirate and/or peripheral blood). CD33 positivity is defined as a ratio of at least 10 (using the anti-CD33 clone P67.6) of the geometric MFI of CD33 for the blast population divided by the MFI of the CD33 background signal of lymphocytes. 2) Informed consent for participation in randomization Ri.
Additional inclusion criteria for the consolidation randomization 1) Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol. 2) Informed consent for participation in randomization Rc.
CRITERIOS DE EXCLUSIÓN
Previous chemotherapy or radiotherapy. This includes patient with therapy-related AML after previous therapy that is known to increase the risk of secondary AML.
Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study.
Patients with known active hepatitis B, hepatitis C, or HIV infection.
Patients for whom informed consent was not obtained.
Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
Myeloid Leukemia of Down syndrome (MLDS).
Acute promyelocytic leukemia (APL).
Additional exclusion criteria for consolidation randomization 1) Patients who previously did not receive chemotherapy according to protocol.
Myelodysplastic syndrome (MDS).
Juvenile Myelomonocytic Leukemia (JMML).
Known intolerance to any of the chemotherapeutic drugs in the protocol.
Evidence of cardiac dysfunction (ejection fraction below 50%, or between 50% and 55% and considered as left ventricular systolic dysfunction by the local (pediatric) cardiologist).
Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use a highly effective method of contraception and, if indicated, monthly pregnancy testing for the duration of study therapy and up to 7 months after the completion of all study therapy.
Additional exclusion criteria for the induction randomization: 1) Hypersensitivity to the active substance of GO or to any of the excipients listed in section 6.1 of the SPC of GO. 2) Patients with FLT3-ITD/NPM1wt. 3) Elevated bilirubin grade 3 according to the CTCAE v5.0.
Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy, and up to 6 months after the completion of all study therapy.
Concomitant administration of any other experimental drug, or concurrent treatment with any other anti-cancer therapy other than specified in this protocol or in one of the trials linked to this Master protocol, when the study objective is affected.
Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study.
Patients with known active hepatitis B, hepatitis C, or HIV infection.
Patients for whom informed consent was not obtained.
Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
Myeloid Leukemia of Down syndrome (MLDS).
Acute promyelocytic leukemia (APL).
Additional exclusion criteria for consolidation randomization 1) Patients who previously did not receive chemotherapy according to protocol.
Myelodysplastic syndrome (MDS).
Juvenile Myelomonocytic Leukemia (JMML).
Known intolerance to any of the chemotherapeutic drugs in the protocol.
Evidence of cardiac dysfunction (ejection fraction below 50%, or between 50% and 55% and considered as left ventricular systolic dysfunction by the local (pediatric) cardiologist).
Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use a highly effective method of contraception and, if indicated, monthly pregnancy testing for the duration of study therapy and up to 7 months after the completion of all study therapy.
Additional exclusion criteria for the induction randomization: 1) Hypersensitivity to the active substance of GO or to any of the excipients listed in section 6.1 of the SPC of GO. 2) Patients with FLT3-ITD/NPM1wt. 3) Elevated bilirubin grade 3 according to the CTCAE v5.0.
Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy, and up to 6 months after the completion of all study therapy.
Concomitant administration of any other experimental drug, or concurrent treatment with any other anti-cancer therapy other than specified in this protocol or in one of the trials linked to this Master protocol, when the study objective is affected.
DESCRIPCIÓN
Overarching objective: To improve the overall EFS for children and adolescents with newly diagnosed AML, compared to NOPHO-DBH AML-2012. Induction randomization: To assess if adding GO to the first induction course results in better early anti-leukemic efficacy in CD33-positive AML patients, compared to no-GO. Consolidation randomization: To demonstrate non-inferiority in disease-free survival of two courses of consolidation therapy, by omitting HA3E, as compared to three courses, in the entire standard-risk group eligible for this randomization.
PALABRAS CLAVE
acute myeloid leukemia, aml, de novo aml, donor lymphocyte infusion, leucemia linfocítica crónica (llc / cll), leukemia, ph + acute lymphoblastic leukemia
