GEMTUZUMAB OZOGAMICIN for Acute Myeloid Leukemia

Inclusion criteria

• {"criterion_text":"- Patients aged 18 years old or more\n- Confirmed diagnosis of R/R AML positive for CD33 antigen as determined locally by immunophenotyping according to routine practice, defined as: - AML refractory to 1 or 2 intensive chemotherapy courses or a treatment by hypomethylating agents (HMAs) - Or AML in first hematologic relapse or progression after front-line therapy, including intensive chemotherapy or hypomethylating agents (HMAs). - Previous treatments with FLT3 inhibitors (other than gilteritinib) are allowed - R/R AML secondary to a prior chemotherapy or radiotherapy for another cancer (tAML) could be included.\n- Presence of a FLT3-ITD mutation (allelic ratio ≥0.05 at last evaluation)* or a FLT3 TKD mutation\n- Patient with no contraindication to gemtuzumab ozogamicin (GO), cytarabine and gilteritinib\n- ECOG performance status ≤2\n- AST and ALT ≤ 2.5 x upper the limit of normal (ULN) and/or total and direct serum bilirubin ≤ 1.5 x ULN unless considered due to leukemia\n- Estimated glomerular filtration rate (GFR) ≥ 50 mL/min according to the formula usually used by the investigator"}

Exclusion criteria

• {"criterion_text":"- Acute promyelocytic leukemia or AML with BCR-ABL1 gene fusion\n- Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate treatment)\n- Active known HBV or HCV hepatitis or positive HIV serology\n- Concurrent therapy with any other investigational agent or cytotoxic drug, within 28 days before starting treatment. Only hydroxyurea ± dexamethasone is permitted for the control of blood counts\n- Current use or anticipated requirement for drugs that are known strong inducers of CYP3 A4/5\n- Current use or anticipated requirement for drugs that are known as strong inhibitors or inducers of P glycoprotein (P-gp), as mentioned in the appendix 14 of the protocol, with the exception of drugs that are considered absolutely essential for the care of the subject\n- Current use or anticipated treatment with concomitant drugs that target 5HT1R or 5HT2BR receptors or sigma non-specific receptor, as mentioned in the appendix 15 of the protocol, with exception of drugs that are considered absolutely essential for the care of the subject\n- Known malabsorption syndrome or other condition that may significantly impair absorption of oral study medications\n- Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study\n- Patient currently receiving one or more inadvisable or prohibited treatments described in section 6.4.2 of the protocol.\n- Secondary AML (sAML) defined by a history of prior myelodysplastic syndrome (MDS) or myeloproliferative syndrome (MPN) including chronic myelomonocytic leukemia (CMML)\n- Patient ineligible for an intensive chemotherapy.\n- Patient with contraindications to the administration of gemtuzumab ozogamicin (GO), cytarabine and gilteritinib. Refer to the SPCs of the molecules mentioned concerning the contraindications, special warnings, precautions for use, dose modifications in the event of toxicity, contraception and monitoring of patients and drugs prohibited or to be used with caution.\n- Proven central nervous system leukemic involvement\n- Prior allogeneic HSCT within the last 6 months and/or history of acute GVHD of grade >1\n- Prior treatment with gemtuzumab ozogamicin within the last 3 months preceding the initiation of the treatment in the present clinical trial\n- Uncontrolled or active malignant disease within prior 12 months (excluding cutaneous basal cell carcinoma, “in-situ” carcinoma of the cervix or breast, or other local malignancy excised)\n- Uncontrolled or significant cardiovascular history or symptoms"}

Primary endpoints

• {"endpoint_text":"- Stage 1 of the study: assessment of safety of the addition of gilteritinib to the AGORA treatment platform Safety of combining gilteritinib with the GO-cytarabine AGORA platform in patients with FLT3-ITD and/or FLT3-TKD mutated R/R AML will be assessed through the identification of dose-limiting toxicities (DLTs) if any.","definition_or_measurement_approach":"Assessment through identification of dose-limiting toxicities (DLTs) during Stage 1."}
• {"endpoint_text":"- Stage 2 of the study: assessment of efficacy of gilteritinib-combined to GO/cytarabine AGORA platform through EFS. The definition of EFS will be adapted to the current real-life setting, including the increasing number of experimental options. Actually, the decision to switch toward another therapy may be influenced by other events than hematologic relapse, like suboptimal tolerance or MRD monitoring or simply availability of new promising options.","definition_or_measurement_approach":"Event-free survival (EFS) adapted to real-life setting; definition may incorporate treatment switch decisions driven by tolerance, MRD monitoring, or availability of new options."}

Secondary endpoints

• {"endpoint_text":"- Response rate, including CR, CRi and CRh*; the overall response rate (ORR) being defined as CR/CRi/CRh rates *: CRi, CR with incomplete hematologic recovery, meaning CR with platelet count <100,000/µL or absolute neutrophil count <1000/µL; CRh, CR with partial hematologic recovery, meaning CR not fulfilling CR or CRi criteria but with platelet count >50,000/µL AND absolute neutrophil count >500/µL.","definition_or_measurement_approach":"ORR defined as CR/CRi/CRh. CRi: CR with platelet <100,000/µL or ANC <1000/µL. CRh: CR with platelet >50,000/µL AND ANC >500/µL."}
• {"endpoint_text":"- Early mortality rates, at day-30","definition_or_measurement_approach":"Mortality rate assessed at day 30 after treatment start."}
• {"endpoint_text":"- Incidence of subsequent allogeneic HSCT, overall and in responding patients specifically","definition_or_measurement_approach":"Incidence proportion of patients receiving subsequent allogeneic hematopoietic stem cell transplantation, overall and among responders."}
• {"endpoint_text":"- Duration of response (DOR), relapse-free survival (RFS) and overall survival (OS)","definition_or_measurement_approach":"Time-to-event measures: DOR, RFS and OS as per standard definitions (time from response to relapse for DOR, time to relapse for RFS, time to death for OS)."}
• {"endpoint_text":"- Subgroup analyses: \t▪\tSubgroups defined by a patient related factor: age (<65 vs ≥65y), \t▪\tSubgroups defined by disease related factors: cytogenetics, mutation profiles (including NPM1 and FLT3-ITD), ELN-risk classification 2022 \t▪\tSubgroups defined by treatment related factor by the performance of a subsequent allogeneic HSCT","definition_or_measurement_approach":"Pre-specified subgroup analyses by age (<65 vs ≥65), cytogenetics, mutation profiles (including NPM1 and FLT3-ITD), ELN-risk 2022, and by subsequent allogeneic HSCT status."}
• {"endpoint_text":"- Safety through the occurrence of (AEs), serious adverse events (SAEs), and treatment emergent adverse events (TEAEs)","definition_or_measurement_approach":"Safety assessed by recording adverse events (AEs), serious adverse events (SAEs), and treatment-emergent adverse events (TEAEs) per standard reporting."}
• {"endpoint_text":"- Patient reported outcome","definition_or_measurement_approach":"Patient-reported outcomes (PROs) collected (instruments referenced in documents such as EORTC QLQ-C30)."}

France

Earliest CTIS Part Ii Submission Date

05-08-2024

Latest Decision Or Authorization Date

16-05-2025

Processing Time Days

284

Number Of Sites

31

Number Of Participants

50

Primary sponsor

Full Name

Centre Antoine Lacassagne

Organisation Type

Health care

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Pfizer","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"Astellas Pharma Europe Ltd","duties_or_roles":"Source of monetary support","organisation_type":""}