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

Overview

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.

Interventions

• Drug Methotrexate
  Methotrexate 12mg given intrathecally within 24 hours prior to blinatumomab administration
• Drug Blinatumomab
  Blinatumomab 28ug/day continuous infusion for 4 weeks

Primary outcome measures

• Number of participants that experienced neurotoxicity during the first cycle of blinatumomab therapy [Time frame: 28 days after first infusion]

Secondary outcome measures (2)

• Number of participants that experienced cytokine release syndrome during the first cycle of blinatumomab therapy [Time frame: 28 days after first infusion]
• Number of participants with a response of complete remission and MRD negativity at the end of cycle 1 [Time frame: 28 days after first infusion]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Northside Hospital — Atlanta

Publications

• Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-8 PMID 28249141
• Gokbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, Diedrich H, Topp MS, Bruggemann M, Horst HA, Havelange V, Stieglmaier J, Wessels H, Haddad V, Benjamin JE, Zugmaier G, Nagorsen D, Bargou RC. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-1531. doi: 10.1182/blood-2017-08-798322. Epub 2018 Jan 22. PMID 29358182
• Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S, Viardot A, Marks R, Diedrich H, Faul C, Reichle A, Horst HA, Bruggemann M, Wessiepe D, Holland C, Alekar S, Mergen N, Einsele H, Hoelzer D, Bargou RC. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphobla PMID 25385737
• Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, Neumann S, Foa R, Litzow M, Ribera JM, Rambaldi A, Schiller G, Bruggemann M, Horst HA, Holland C, Jia C, Maniar T, Huber B, Nagorsen D, Forman SJ, Kantarjian HM. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a PMID 25524800
• Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, Noppeney R, Viardot A, Hess G, Schuler M, Einsele H, Brandl C, Wolf A, Kirchinger P, Klappers P, Schmidt M, Riethmuller G, Reinhardt C, Baeuerle PA, Kufer P. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science. 2008 Aug 15;321(5891):974-7. doi: 10.1126/science.1158545. PMID 18703743
• Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, Stelljes M, Schaich M, Degenhard E, Kohne-Volland R, Bruggemann M, Ottmann O, Pfeifer H, Burmeister T, Nagorsen D, Schmidt M, Lutterbuese R, Reinhardt C, Baeuerle PA, Kneba M, Einsele H, Riethmuller G, Hoelzer D, Zugmaier G, Bargou RC. Targeted therapy with the T-cell-engaging antibody blinatumom PMID 21576633
• Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A. Complete Hematologic and Molecular Response in Adult Patients With Relapsed/Refractory Philadelphia Chromosome-Positive B-Precursor Acute Lymphoblastic Leukemia Following Treatment With Blinatumomab: Results From a Phase II, Single-Arm, Multi PMID 28355115
• Jain T, Litzow MR. No free rides: management of toxicities of novel immunotherapies in ALL, including financial. Blood Adv. 2018 Nov 27;2(22):3393-3403. doi: 10.1182/bloodadvances.2018020198. PMID 30482769

Identifiers

NCT: NCT05519579 · NSH 1354

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗