relapsed or refractory CD33-positive acute myeloid leukaemia (AML) MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Mylotarg®
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: GEMTUZUMAB OZOGAMICIN
CAS Number: 22057
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Refractory or relapsed (ie, bone marrow blasts =5%) CD33-positive AML. 2. Age=12 years. 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2. 4. Initial peripheral white blood cells (WBC) counts =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Patients with prior treatment with GO. 2. Patients with prior history of VOD/SOS. 3. Prior HSCT is not allowed, if it was conducted within 2 months prior to study enrollment. 4. Patients with known active central nervous system (CNS) leukemia. 5. Uncontrolled or active infectious status. 6. Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism. 7. Uncontrolled cardiac dysrhythmias of NCI CTCAE Grade 2, uncontrolled atrial fibrillation of any grade. 8. Sero-positivity to human immunodeficieny virus (HIV). 9. Active hepatitis B or hepatitis C infection (see Appendix 2 of the protocol). 10. Chemotherapy, radiotherapy, or other anti-cancer therapy (except hydroxyurea as cytoreduction) within 2 weeks prior to enrollment in the study. 11. Major surgery within 4 weeks prior to enrollment. 12. Diagnosis of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. 13. QTc interval >470 milliseconds (msec) using the Fridericia (QTcF) (based on the mean value of the triplicate electrocardiograms [ECGs]), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP). 14. The use of medications known to predispose to Torsades de Pointes within 2 weeks prior to enrollment (see Appendix 4 of the protocol). 15. History of allergic reactions attributed to compounds of similar chemical or biologic composition to GO. 16. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study. 17. Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation. 18. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. 19. Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilli
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of GO on the QTc interval; Secondary Objective: To characterize the PK of single-agent GO following the fractionated regimen (ie, 3 mg/m² on Days 1, 4, and 7). - To assess the safety of GO with fractionated dosing of 3 mg/m2. - To assess the immunogenicity of GO. - To assess response and overall survival. Exploratory Objectives: - To assess CD33 saturation and relation to the fractionated regimen of GO. - To assess CD33 expression by central lab immunophenotyping. - To assess metabolites after treatment with GO. - To collect banked biospecimens for exploratory research, unless prohibited by local regulations or ethics committee decision. ;Primary end point(s): Maximum change from baseline in corrected QT interval (QTc).; Timepoint(s) of evaluation of this end point: Triplicate ECGs will be performed at screening, baseline (prior to dose on Day 1) and on each day of dosing (Days 1, 4, and 7 of at cycle). ECGs will be paired with PK blood sampling and collected immediately prior to the PK blood sample collection, such that the blood sample is collected at the nominal planned time. Additional ECGs will be performed as clinically indicated for patient safety monitoring and documentation stored in the source documents. All ECGs will be sent to the ECG core laboratory for independent reading and interpretation. Additional information on timepoints collection is provided in the Schedule of activities Table 2 (page 16) and Assessment of Primary Endpoints (section 7.1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PK parameters: clearance and volume of distribution. - Adverse events (AEs) and abnormal laboratory findings. - Incidence of anti-drug antibody (ADA)/neutralizing antibodies (NAb). - Response: complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) achieved after GO. - Overall Survival. Exploratory endpoints: - CD33 site saturation levels in peripheral blood (PB) in relation to GO. - CD33 expression in bone marrow or peripheral blood. - Metabolic profiling in plasma and urine. - Collection of banked biospecimens unless prohibited by local regulations or ethics committee decision. Additional information on collection and potential use is provided in the Banked Biospecimens section. ; Timepoint(s) of evaluation of this end point: - Samplings for PK will be collected at several days and times during Cycle 1 (Day 1: H0, H1, H2, H4, H6 and H24; Day 4: H0 and H2; Day 7: H0, H2, H4 and H6; Day 10; Day 15 and D21) and during Cycle 2 (Day 1: H0, H2; Day 7: H0, H2, H6; Day 15; Day 21; End of Treatment (EoT)). - Samplings for ADA/Nab will be collected at baseline, at Day 15 and Day 21 of each cycle and at EoT. - Efficacy evaluation and determination of remission status by blood and bone marrow aspiration (and biopsy if applicable) will be conducted at the end of each cycle. Additional information on timepoints collection is provided in the Schedule of activities Table 2 (page 16) and Assessment of secondary Endpoints (sections 7.2, 7.3, 7.4, 7.5 and 7.6). | — |
Countries
Canada, Germany, Hungary, Poland, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed