Obinutuzumab Versus Rituximab for Acute Lymphoblastic Leukemia/PALG ALL7 OVERALL

Study Overview
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Brief Summary
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A multicenter, prospective, randomized and controlled study to compare the efficacy and safety of obinutuzumab and rituximab in adult ALL patients with CD20 expression.Study population is 124 patients (62 in each study group).

Official Title
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Efficacy and Safety of Obinutuzumab Versus Rituximab in Combination With Chemotherapy for Adult Patients With Newly Diagnosed CD20-positive Acute Lymphoblastic Leukemia

Conditions
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CD20-positive Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Obinutuzumab
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years. Newly diagnosed Acute lymphoblastic leukemia with CD20 expression on at least 20% of blasts. Signed written informed consent. Adequate contraception in case of women with child-bearing potential Exclusion Criteria: Lymphoblastic lymphoma with bone marrow blasts<20%. Patients with a history of chronic myeloid leukemia or other myeloproliferative disease. Major surgery within 4 weeks before enrollment. Impaired cardiac function: ejection fraction <40% on echocardiography, QTc interval > 450 ms on baseline electrocardiogram. Myocardial infarction within 6 months prior to starting study; other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias). Active infection e.g. hepatitis B virus, hepatitis C virus, human immunodeficiency virus Other concurrent severe and/or uncontrolled medical conditions: patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease. Serum creatinine > 2 times the upper normal limit of the laboratory, total bilirubin> 2.5 upper normal limit unless related to Acute lymphoblastic leukemia, aspartate aminotransferase or alanine aminotransferase > 5 upper normal limit, unless related to Acute lymphoblastic leukemia Intolerance to treatment with monoclonal antibody. Positive pregnancy test (beta human chorionic gonadotropin) for women of childbearing age. Inability to obtain written informed consent. Inability to comply with regular monitoring.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obinutuzumab<br>Patients in reference arm (Arm A) will receive rituximab. Patients in experimental arm (Arm B) will receive obinutuzumab instead of rituximab in the same time-points. | Drug: Obinutuzumab<br>* Chemotherapy will be conducted according to PALG ALL7 protocol, which is considered a standard of care in Poland. Patients in experimental arm will receive obinutuzumab .Obinutuzumab: 1000 mg i.v. (first infusion divided into 100 mg on d. 1 and 900 mg on d. 2).<br>|
| Active Comparator: Rituximab<br>Patients in reference arm (Arm A) will receive rituximab. Patients in experimental arm (Arm B) will receive obinutuzumab instead of rituximab in the same time-points. | Drug: Rituximab<br>* Chemotherapy will be conducted according to PALG ALL7 protocol, which is considered a standard of care in Poland.The protocol includes the use of rituximab in combination chemotherapy. Rituximab: 375 mg/m2 intravenously (i.v.)<br>* Other names: Activ comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving complete remission with Minimal Residual Disease level <0.1% of bone marrow cells after one course of induction treatment. |  | assessed between days 33-34 since start of Induction I | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients achieving complete remission with Minimal Residual Disease level <0.01% of bone marrow cells after consolidation. |  | assessed between days 20-28 since start of last course of consolidation | 
| complete remission rate after Induction I |  | assessed between days 33-34 since start of Induction I | 
| Overall complete remission |  | in 24month follow up | 
| Probability of overall survival |  | in 24 month follow up | 
| Probability of relapse-free survival |  | in 24 month follow up | 
| Probability of event-free survival |  | in 24 month follow up | 
| Cumulative incidence of relapse |  | in 24 month follow up | 
| Rate of adverse events |  | in 24 month follow up |