Sequential Chemotherapy and Blinatumomab to Improve MRD Response and Survival in Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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The present study aims at analyzing the response to treatment of adult patients homogeneously treated with supportive care, chemotherapy and blinatumomab.

Detailed Description
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Eligible patients with CD19+ Ph- BCP ALL (Philadelphia-negative B-cell precursor acute lymphoblastic leukemia) will receive homogeneous supportive care, chemotherapy and blinatumomab immunotherapy, and will be homogeneously analyzed for response at prefixed time points from induction day 1. For risk-oriented therapy, patients in complete remission (CR) will be stratified by risk class according to the diagnostic characteristics and MRD (minimal residual disease) study results during early consolidation.

Official Title
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National Treatment Program With Sequential Chemotherapy and Blinatumomab to Improve Minimal Residual Disease Response and Survival in Philadelphia Chromosome-Negative B-Cell Precursor Adult Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoid Leukemia, Philadelphia Chromosome-Negative B-Cell Precursor

Intervention / Treatment
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* Drug: Chemotherapy + Blinatumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent according to ICH/EU/GCP and national local laws. Age 18-65 years. A diagnosis of untreated Ph- CD19+ BCP ALL is required, either de novo or secondary to chemo-radiotherapy for another cancer. Pre-treatment with low-dose corticosteroids in patients presenting with hyperleukocytosis is allowed. Before enrolment and pre-phase is allowed only in patients presenting with severe, potentially life-threatening disease-related clinical symptoms. All diagnostic procedures need to be performed on freshly obtained bone marrow (BM) and peripheral blood (PB) samples. Full cytological, cytochemical, immunophenotypic, cytogenetic and molecular disease characterization according to the EGIL and WHO classifications. BM and PB sampling for MRD evaluations study. Detailed indications on patient registration, storage of representative diagnostic material and diagnostic work-up, including the shipping of samples for the diagnostic work-up and MRD follow-up studies are given in Appendix A. An ECOG performance status 0-2, unless a performance of 3 is unequivocally caused by the disease itself, (and not by pre-existing comorbidities,) and is considered and/or documented to be reversible following the application of anti-leukemic therapy and appropriate supportive measures. Exclusion Criteria: Diagnosis of Burkitt's leukemia/lymphoma, CD19- BCP ALL, Ph+ ALL, T-ALL, lymphoblastic lymphoma (BM involvement by blast cells <25%). Active CNS leukemia documented by diagnostic lumbar puncture on days -1 to -5 prior to the first blinatumomab administration, or any other clinical sign or symptom ascribable to symptomatic/documented CNS disease at time of each planned blinatumomab course. Down's syndrome. A pre-existing, uncontrolled pathology such as heart failure (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrhythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to ALL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL), and severe neuropsychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan. N.B. For altered liver and kidney function tests, eligibility criteria can be reassessed at 24-96 hours, following the institution of adequate supportive measures. Presence of serious, active, uncontrolled infections. Pre-existing HIV positive serology (i.e. already known before enrolment). If HIV positivity is detected after enrolment, the patient is put off study. A history of cancer that is not in a remission phase following surgery and/or radiotherapy and/or chemotherapy, with a life expectancy <1 year. Pregnancy declared by the patient, unless a decision is taken with the patient to induce a therapeutic abortion in order to carry on with the ALL therapy. A pregnancy test is performed at diagnosis, but does not preclude the enrolment into study. Fertile patients will be advised to adopt contraceptive methods while on treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy + Blinatumomab<br>Treatment sequence consists of eight chemotherapy courses and two blinatumomab courses. Patients not in CR after chemotherapy course 2 will go off-study. | Drug: Chemotherapy + Blinatumomab<br>* Chemotherapy cycles are administered at 21-28 days intervals and each blinatumomab course is 28-day long.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients that obtain a negative Minimal Residual Disease (MRD) |  | At week 14 from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients in complete remission (CR) |  | At 32 months from study entry | 
| Number of patients that reach disease-free survial |  | At 32 months from study entry | 
| Number of patients that relapse |  | At 32 months from study entry | 
| Number of patients that dye due to treatment | Treatment-related mortality | At 32 months from study entry | 
| Number of serious adverse events | Safety | At 32 months from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoid Leukemia, Philadelphia Chromosome-Negative B-Cell Precursor, Adults, Minimal residual disease, Blinatumomab