Feasibility and Effectiveness of Inotuzumab Ozogamicin in B-Cell Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a multi-center, phase 2A exploratory study of feasibility and effectiveness of Inotuzumab Ozagomicin in adult patients with Acute Lymphoid Leukemia (ALL) with positive minimal residual disease before any hematopoietic stem cell transplantation. The study is divided in two cohorts; cohort 1 will enroll 38 Ph+ patients, cohort 2 will enroll 38 Ph- patients, as defined with statistical analysis. The two cohorts will have the same treatment, with the exception of short term and long term maintenance.

Official Title
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A Phase IIA Study of Feasibility and Effectiveness of Inotuzumab Ozogamicin (IO) in Adult Patients With B-Cell Acute Lymphoblastic Leukemia With Positive Minimal Residual Disease Before Any Hematopoietic Stem Cell Transplantation

Conditions
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Acute Lymphoid Leukemia

Intervention / Treatment
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* Drug: Inotuzumab Ozogamicin (IO)
* Drug: Inotuzumab Ozogamicin (IO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ph+ ALL with p190 or p210 detectable and measurable (at least 10-4 x10000 ABL) after at least 3 months of any therapy, or the failure of at least 2 TKI. Ph- ALL with detectable and measurable IG specific transcript after at least 2 courses of previous therapy. Age ≥ 18 years old. ECOG ≤ 2. Exclusion Criteria: More than 5% of BM blasts. WHO performance status ≤ 50% (Karnofsky) or ≥ 3 (ECOG). 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 co-morbidity will be carefully evaluated for enrolment. Ongoing or active infections. Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL). Clinically significant, uncontrolled, or active cardiovascular disease. 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 who are pregnant or breastfeeding 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). Postmenopausal women must be amenorrheic 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. Patients unwilling or unable to comply with the protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study is divided in two cohorts; cohort 1 will enroll 38 Ph+ patients, cohort 2 will enroll 38 Ph- patients, as defined with statistical analysis. The two cohorts will have the same treatment, with the exception of short term and long term maintenance.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1 will entroll 38 Ph+ patients | Drug: Inotuzumab Ozogamicin (IO)<br>* After course 1 MRD will be evaluated: - patients MRD negative will enter into short maintenance or long maintenance according to investigator choice. After 4 to 12 weeks in short maintenance patient will undergo SCT, otherwise, patients will enter long maintenance.<br>|
| Experimental: Cohort 2<br>Cohort 2 will enroll 38 Ph- patients | Drug: Inotuzumab Ozogamicin (IO)<br>* After course 2 MRD will be evaluated; patients MRD negative will enter into short maintenance or long maintenance by investigator choice. After 4 to 12 weeks in short maintenance patient will undergo SCT, otherwise, patients will enter long maintenance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients obtaining a negative Minimal Residual Disease (MRD) |  | Two years after study entry. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients alive |  | Two years from start of treatment. | 
| Number of adverse events in MRD positive patients |  | Two years after study entry. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoid Leukemia, Inotuzumab Ozogamicin