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

NCT05519579 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NSH 1354
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of participants that experienced cytokine release syndrome during the first cycle of blinatumomab therapy

  28 days after first infusion

• Number of participants with a response of complete remission and MRD negativity at the end of cycle 1

  28 days after first infusion

Study Arms (1)

Intrathecal chemotherapy before blinatumomab

EXPERIMENTAL

Drug: Methotrexate; Drug: Blinatumomab

Interventions

Methotrexate DRUG

Methotrexate 12mg given intrathecally within 24 hours prior to blinatumomab administration

Intrathecal chemotherapy before blinatumomab

Blinatumomab DRUG

Blinatumomab 28ug/day continuous infusion for 4 weeks

Intrathecal chemotherapy before blinatumomab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northside Hospital, Inc.: lead

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Related Publications (9)

• 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):836-847. doi: 10.1056/NEJMoa1609783.

  PMID: 28249141 BACKGROUND

• 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 BACKGROUND

• 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 lymphoblastic leukemia. J Clin Oncol. 2014 Dec 20;32(36):4134-40. doi: 10.1200/JCO.2014.56.3247. Epub 2014 Nov 10.

  PMID: 25385737 BACKGROUND

• 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 multicentre, single-arm, phase 2 study. Lancet Oncol. 2015 Jan;16(1):57-66. doi: 10.1016/S1470-2045(14)71170-2. Epub 2014 Dec 16.

  PMID: 25524800 BACKGROUND

• 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 BACKGROUND

• 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 blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011 Jun 20;29(18):2493-8. doi: 10.1200/JCO.2010.32.7270. Epub 2011 May 16.

  PMID: 21576633 BACKGROUND

• 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, Multicenter Study. J Clin Oncol. 2017 Jun 1;35(16):1795-1802. doi: 10.1200/JCO.2016.69.3531. Epub 2017 Mar 29.

  PMID: 28355115 BACKGROUND

• 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 BACKGROUND

• Shah NN, Johnson BD, Fenske TS, Raj RV, Hari P. Intrathecal chemotherapy for management of steroid-refractory CAR T-cell-associated neurotoxicity syndrome. Blood Adv. 2020 May 26;4(10):2119-2122. doi: 10.1182/bloodadvances.2020001626. No abstract available.

  PMID: 32407473 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Methotrexate; blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Melhem Solh, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Caitlin Guzowski

CONTACT

404-851-8523; caitlin.guzowski@northside.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2022
• First Posted: August 29, 2022
• Study Start: June 30, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (1)