Trial aimed at examinate the functionality and effectiveness of the drug "IO" in adult patients with a rare form of cancer that affect the cells from which the white blood cells (cells present in the blood) originate before being subjected to a medical procedure used in hematology known as transplantation, which leads to the replacement of the cells from which the blood originates.

Phase 2

Recruiting

• Conditions: Acute B-cell Lymphoblastic Leukemia with minimal residual positive disease prior to haematopoietic stem cell transplantation in adult patients

• Registration Number: 2023-510516-39-00
• Lead Sponsor: Fondazione Gimema Franco Mandelli Onlus

Brief Summary

The primary objective of the study is to determine effectiveness of Inotuzumab in obtaining MRD negativity in MRD positive ALL patients.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-12-03
• Last Update Posted: 2024-12-03

Recruitment & Eligibility

• Status: Ongoing, recruiting
• Sex: Not specified
• Target Recruitment: 76

Inclusion Criteria

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

For females of childbearing potential, a negative pregnancy test must be documented at Screening

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

Signed written informed consent according to ICH/EU/GCP and national local laws.

Blasts at the diagnosis or in any timepoint had to be CD22+

To have a measurable BCR-ABL1 fusion transcript (cohort 1) or a measurable IG/TCR specific rearrangement (cohort 2)

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)

and to not have more than 5% of bone marrow blasts. Patients has to be in 1st or 2nd complete remission.

Patients = 18 years old with no upper age limit

Patients with a life expectancy >12 weeks

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

Adequate pancreatic function as defined by the following criterion: a. serum lipase and amylase =1.5 × ULN

Exclusion Criteria

More than 5% of BM blasts

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

Creatinine level > 2.5mg/dl or Glomerular Filtration Rate (GFR) < 20 ml/min or proteinuria > 3.5 g/day

Documented inherited protrombotic disorders

Patients who have received any investigational drug = 4 weeks

Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy;

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

Patients that have received Inotuzumab or Anti CD22 directed therapies before

Patients with known hereditary coagulopathy

Patient that received during their life diagnosis of VOD or had ongoing VOD

Patients with hypersensitivity to the active substance or to any of the excipients (Sucrose, Polysorbate 80, Sodium chloride, tromethamine)

WHO performance status = 50% (Karnofsky) or = 3 (ECOG)

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

Patients unwilling or unable to comply with the protocol

Active HBV or HCV hepatitis, or AST/ALT = 2.5 x ULN and bilirubine = 1.5 x ULN

Evidence of liver fibrosis, portal hypertension or other clinically relevant liver abnormalities at screening liver ultrasonography

History of alcohol abuse

Burkitt lymphoma and active CNS leukemia. Patients with previuos neurological toxicitiy as well comorbidity will be carefully evaluated for enrolment

Ongoing or active infections

Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Primary end point is % of MRD negativity after course 2 (or course 1 if will be performed only course1).		Primary end point is % of MRD negativity after course 2 (or course 1 if will be performed only course1).

Secondary Outcome Measures

Name	Time	Method
Molecular Disease Progression: defined as the rise of more than 2 log in MRD from any previous determination		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.		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.		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.		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.		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.		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.		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.		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.		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.		VOD occurred during or after protocol or transplant procedures for up to 2 years.

Trial Locations

Locations (43)

Azienda Ospedaliera Santa Croce E Carle; 🇮🇹 Cuneo, Italy

Azienda Ospedaliera Universitaria Senese; 🇮🇹 Siena, Italy

Azienda Ospedaliera di Padova; 🇮🇹 Padova, Italy

Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga; 🇮🇹 Orbassano, Italy

Azienda Socio Sanitaria Territoriale Papa Giovanni Xxiii; 🇮🇹 Bergamo, Italy

Azienda Ospedaliero-Universitaria Policlinico Umberto I; 🇮🇹 Rome, Italy

ULSS3 SERENISSIMA - Ospedale dell'Angelo di Mestre; 🇮🇹 Italy

Azienda Sanitaria Locale Di Pescara; 🇮🇹 Pescara, Italy

Casa Sollievo Della Sofferenza; 🇮🇹 San Giovanni Rotondo, Italy

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Azienda Ospedaliera Santa Croce E Carle

🇮🇹Cuneo, Italy

Daniele Mattei

Site contact

+390171642478

mattei.d@ospedale.cuneo.it