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

Обзор

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (2)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

США · 1 центр

• Northside Hospital — Atlanta

Публикации

• 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

Идентификаторы

NCT: NCT05519579 · NSH 1354

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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