Acute B-cell Lymphoblastic Leukemia with minimal residual positive disease prior to haematopoietic stem cell transplantation in adult patients MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: NA
Product Name: Inotuzumab Ozogamicina (IO)
Product Code: [PF-05208773]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Inotuzumab Ozogamicin (IO)
Current Sponsor code: NA
Sponsors
FONDAZIONE GIMEMA (GRUPPO ITALIANO MALATTIE EMATOLOGICHE DELL' ADULTO) FRANCO MANDELLI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients must meet all the following criteria for study entry: 1. To be classified as having ALL according to WHO classification of haematological neoplasms, patients must have >20% blasts in bone marrow at the time of diagnosis; 2. Blasts at the diagnosis or in any timepoint had to be CD22+; 3. To have a measurable BCR-ABL1 fusion transcript (cohort 1) or a measurable IG/TCR specific rearrangement (cohort 2); 4. To have any measurable MRD positivity after at least: a. 3 months of therapy for Ph+ ALL, or the failure of at least 2nd line TKI (cohort 1) b. 2 courses of therapy for Ph- ALL (cohort 2); 5. and to not have more than 5% of bone marrow blasts. Patients has to be in 1st or 2nd complete remission; 6. Patients = 18 years old with no upper age limit; 7. Patients with a life expectancy >12 weeks; 8. Adequate hepatic function as defined by the following criteria: a. total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert’s syndrome b. alanine aminotransferase (ALT) =2.5 × ULN c. aspartate aminotransferase (AST) =2.5 × ULN; 9. Adequate pancreatic function as defined by the following criterion: a. serum lipase and amylase =1.5 × ULN; 10. For females of childbearing potential, a negative pregnancy test must be documented at Screening; 11. Female and male patients who are fertile should use an effective form of contraception with their sexual partners from screening through 4 months after the end of treatment. As a precautionary measure, breast-feeding should be discontinued during treatment with Inotuzumab and should not be restarted after discontinuation of Inotuzumab. Male patients must agree to refrain from sperm donation, from initial treatment administration until 12 months after the last dose of study drug. 12. Signed written informed consent according to ICH/EU/GCP and national local laws. 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 76 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. More than 5% of BM blasts; 2. WHO performance status = 50% (Karnofsky) or = 3 (ECOG); 3. Active HBV or HCV hepatitis, or AST/ALT = 2.5 x ULN and bilirubine = 1.5 x ULN; 4. Evidence of liver fibrosis, portal hypertension or other clinically relevant liver abnormalities at screening liver ultrasonography; 5. History of alcohol abuse; 6. Burkitt lymphoma and active CNS leukemia. Patients with previuos neurological toxicitiy as well comorbidity will be carefully evaluated for enrolment; 7. Ongoing or active infections. 8. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL). 9. Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: a. any history of myocardial infarction, stroke, or revascularization b. unstable angina or transient ischemic attack within 6 months prior to enrollment c. congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment d. history of clinically significant (as determined by the treating physician) atrial arrhythmia e. any history of ventricular arrhythmia f. any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism; 10. Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control; 11. Creatinine level > 2.5mg/dl or Glomerular Filtration Rate (GFR) 3.5 g/day; 12. Documented inherited protrombotic disorders; 13. Patients who have received any investigational drug = 4 weeks; 14. Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy; 15. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention or with a life expectancy due to other malignancy <6 months; 16. Patients that have received Inotuzumab or Anti CD22 directed therapies before 17. Patients with known hereditary coagulopathy; 18. Patient that received during their life diagnosis of VOD or had ongoing VOD; 19.Patients with hypersensitivity to the active substance or to any of the excipients (Sucrose, Polysorbate 80, Sodium chloride, tromethamine); 20. Patients who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control (women of childbearing potential must have a negative serum pregnancy test within 48 hrs prior to administration of induction therapy). Post menopausal women must be amenorrhoic for at least 12 months to be considered of non-childbearing potential. Male and female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 4 months following discontinuation of study drugs. Fertile patients will be advised to adopt contraceptive methods while on treatment; 21. Patients unwilling or unable to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine effectiveness of Inotuzumab in obtaining MRD negativity in MRD positive ALL patients.;Secondary Objective: The study aim is to: - Establish survival of the treatment population; - Define treatment safety and incidence of adverse events in MRD positive population; - Define the number of patient that will have a bridge to transplant with Inotuzumab (considering only patients that could be transplanted).;Primary end point(s): Primary end point is % of MRD negativity after course 2 (or course 1 if will be performed only course1).;Timepoint(s) of evaluation of this end point: From enrollment until the end of course 2 (or course 1 if only course 1 is run). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Molecular Disease Progression: defined as the rise of more than 2 log in MRD from any previous determination - Disease Progression: this is also equivalent to Treatment Failure, Lack of Efficacy, or No Response. - Overall Survival (OS), defined as the number of days between the first study drug administration and death from any cause or lost to follow up. - Event Free Survival (EFS), defined as the number of days between the first study drug administration and any event including disease progressionor death. - DFS (Disease Free Survival), defined as the interval between the date of response achievement and the date of death, relapse or last follow-up. - Incidence time and nature of any adverse event. - Severe effect related to treatment safety is defined as an adverse event occurring within the first cycle, judged to be related to treatment and meeting any of the following criteria: o Grade 3 non-hematological toxicity lasting more than 7 days. o Grade 4 non-hematological toxicity. - Incidence, severity, seriousness and treatment-causality of Treatment Emergent Signs and Symptoms. - Frequency of clinically significant abnormalities in physical examination, safety laboratory tests, vital signs and 12-Lead ECG. - VOD occurred during or after protocol or transplant procedures for up to 2 years.;Timepoint(s) of evaluation of this end point: Estimations will be provided with Kaplan Meyer model. Safety will be reported with descriptive statistics. The detection time is approximately three years. | — |
Countries
Italy
Contacts
Public ContactCentro Dati GIMEMA
Fondazione GIMEMA Franco Mandelli ONLUS
Outcome results
None listed