Intrathecal Chemoprophylaxis to Prevent Neurotoxicity Associated With Blinatumomab Therapy for Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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Changing the schedule of intrathecal chemotherapy to be given before and during blinatumomab will maintain the anti-leukemic effects of this drug while at the same time adding the benefit of limiting the neurotoxicity associated with cytokine release.

Official Title
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Intrathecal Chemoprophylaxis to Prevent Neurotoxicity Associated With Blinatumomab Therapy for Acute Lymphoblastic Leukemia

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Blinatumomab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults receiving first cycle of blinatumomab for relapse/refractory or MRD-positive B-cell Acute Lymphoblastic Leukemia Adequate renal and hepatic function Negative for HIV Negative serum pregnancy test, if applicable ECOG 0-2 Exclusion Criteria: Active CNS involvement by ALL Relative CNS disorders (seizure, paresis, aphasia, Cerebrovascular ischemia/hemorrhage, severe brain injury, dementia, Parkinson's, cerebellar disease, psychosis, coordination or movement disorder) Contraindication to receive intrathecal methotrexate Prior treatment with blinatumomab Active malignancy other than ALL Active infection or any other concurrent disease or medical condition that was deemed to interfere with the conduct of the study as judged by the investigator

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intrathecal chemotherapy before blinatumomab<br> | Drug: Methotrexate<br>* Methotrexate 12mg given intrathecally within 24 hours prior to blinatumomab administration<br>Drug: Blinatumomab<br>* Blinatumomab 28ug/day continuous infusion for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that experienced neurotoxicity during the first cycle of blinatumomab therapy | Record occurrence and severity of neurotoxicity based on CTCAE criteria | 28 days after first infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that experienced cytokine release syndrome during the first cycle of blinatumomab therapy | Record occurrence and severity of cytokine release syndrome based on CTCAE criteria | 28 days after first infusion | 
| Number of participants with a response of complete remission and MRD negativity at the end of cycle 1 | Conduct disease restaging assessments, such as bone marrow biopsies and lumbar punctures, to determine response to treatment | 28 days after first infusion |