Acute Myeloid Leukemia CD123 + or with BPDCN immunophenotype 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)
Conditions
Interventions
Product Name: Elzonris™ (tagraxofusp-erzs)
Product Code: [NA]
Pharmaceutical Form: Solution for injection
CAS Number: 2055491-00-2
Current Sponsor code: NA
Concentration unit: µg/ml microgram(s)/milli
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has evidence of AML in the peripheral blood and/or bone marrow with either BPDCN-IF [CD123/CD4/CD56 (+)] or with AML that is CD123+ but negative for either, or both, CD4 and CD56. 2. The patient is =18 years old. 3. The patient must be refractory to at least one previous line of conventional therapy (either high dose therapy or hypomethylating agents) or relapsed after receiving conventional therapy (a maximum of two previous line of therapy is admitted). 4. The patient has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 to 2. 5. The patient has adequate baseline organ function, including cardiac, renal, and hepatic function: a. Left ventricular ejection fraction (LVEF) =institutional lower limit of normal as measured by multigated acquisition (MUGA) scan or 2-dimensional (2-D) echocardiography(ECHO) within 21 days before start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG). b. Serum creatinine =1.5 mg/dL (133 µmol/L). c. Serum albumin =3.2 g/dL (32 g/L) (albumin infusions are not permitted to enable eligibility). d. Bilirubin =1.5 mg/dL (26 µmol/L). e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times the upper limit of normal (ULN). 6. If the patient is a woman of childbearing potential (WOCBP), she must have a negative serum or urine pregnancy test at screeningwithin 1 week before treatment. 7. The patient has signed informed consent before initiation of any study-specific procedures or treatment. 8. The patient is able to adhere to the study visit schedule and other protocol requirements, including follow-up for survival assessment. 9. The patient (male and female) agrees to use acceptable contraceptive methods for the duration of time on the study and continue to use acceptable contraceptive methods for 1 week after the last infusion of tagraxofusp. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. The patient has a diagnosis of acute promyelocytic leukemia (APL; FAB subtype M3). 2. The patient has persistent clinically significant toxicities of Grade=2 from previous chemotherapy (excluding alopecia, nausea, fatigue, and liver function tests [as mandated in the inclusion criteria]). 3. The patient has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry. 4. The patient has received treatment with an investigational agent within 14 days of study entry. 5. The patient has previously received treatment with tagraxofusp. 6. The patient has an active malignancy and/or cancer history (excluding antecedent MDS) that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) with substantial potential for recurrence and/or ongoing active malignancy will be evaluated on a case by case basis. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organconfined prostate cancer with no evidence of progressive disease. 7. The patient has clinically significant cardiovascular disease (eg, uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months before study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication). 8. The patient has uncontrolled, clinically significant pulmonary disease (eg, chronic obstructive pulmonary disease, pulmonary hypertension) that, in the opinion of the Investigator, would put the patient at significant risk for pulmonary complications during the study. 9. The patient has known active or suspected central nervous system (CNS) leukemia. If suspected, CNS leukemia should be ruled out with relevant imaging and/or examination of cerebrospinal fluid. 10. The patient is receiving immunosuppressive therapy – with the exception of low-dose prednisone (=10 mg/day) – for treatment or prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment or prophylaxis for GVHD, the treatment(s) must have been discontinued at least 14 days before study treatment and there must be no evidence of Grade =2 GVHD. 11. The patient has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements. 12. The patient is pregnant or breastfeeding. 13. The patient has known positive status for human immunodeficiency virus or active or chronic hepatitis B or hepatitis C (Patients with positive serology for HBV can be enrolled and must receive antiviral prophylaxis – i.e lamivudine or entcavir). 14. The patient is oxygen-dependent. 15. The patient has any medical condition that, in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities. 16. The patient has AML and requires more than 1 g/day of hydroxyurea. (Hydroxyureaispermittedatdoses of =1 g/day.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the activity of tagraxofusp, in terms PR, CR or CRi, in patients with CD123+ or BlasticPlasmacytoid Dendritic Cell Neoplasm-like phenotype (BPDCN-IF) Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML).;Secondary Objective: To estimate in the two cohorts (BPDCN-IF and CD123+ AML): 1) Safety 2) Overall Survival (OS) 3) Event Free Survival (EFS) 4) Disease Free Survival (DFS) 5) Cumulative incidence of relapse (CIR) 6) Response rate and survival outcomes according to baseline clinical and biological characteristics 7) Evaluation of the activity of the treatment as a bridge to transplant;Primary end point(s): Evaluate the activity of tagraxofusp in patients with CD123+ or BlasticPlasmacytoid Dendritic Cell Neoplasm-like phenotype (BPDCN-IF) Relapsed/Refractory (R/R) Acute Myeloid Leukemia(AML). The activity of the study drug will be evaluated in terms of PR, CR or CRi after four cycles.;Timepoint(s) of evaluation of this end point: After 4 cycles of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To estimate in the two cohorts (BPDCN-IF and CD123+ AML): 1) Rate of adverse events (AE) and serious AE (SAE) 2) Overall Survival (OS) at 24 months 3) Event Free Survival (EFS) at 24 months 4) Disease Free Survival (DFS) at 24 months from response assessment 5) Cumulative incidence of relapse (CIR) at 24 months from response assessment 6) Response rate, OS, EFS, DFS and CIR according to baseline characteristics such as age, performance status, white blood cell (WBC), morphology, cytogenetic and molecular features. 7) Percentage of patients undergoing allogeneic stem cell transplantation in MRD-negative CR;Timepoint(s) of evaluation of this end point: At 24 months. | — |
Countries
Italy
Contacts
Public ContactCentro Dati Dati
Fondazione GIMEMA
Outcome results
None listed