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

NCT ID: NCT05519579

Last Updated: 2025-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-06-30

Study Completion Date

2025-12-01

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.

Detailed Description

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Conditions

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Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Intrathecal chemotherapy before blinatumomab

Group Type EXPERIMENTAL

Methotrexate

Intervention Type DRUG

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

Blinatumomab

Intervention Type DRUG

Blinatumomab 28ug/day continuous infusion for 4 weeks

Interventions

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Methotrexate

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

Intervention Type DRUG

Blinatumomab

Blinatumomab 28ug/day continuous infusion for 4 weeks

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northside Hospital, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Melhem Solh, MD

Role: PRINCIPAL_INVESTIGATOR

Blood and Marrow Transplant Group of Georgia

Locations

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Northside Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Caitlin Guzowski

Role: CONTACT

404-851-8523

Facility Contacts

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Caitlin Guzowski, MBA, MHA

Role: primary

404-851-8523

References

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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.

Reference Type BACKGROUND
PMID: 28249141 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29358182 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25385737 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25524800 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18703743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21576633 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28355115 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30482769 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32407473 (View on PubMed)

Other Identifiers

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NSH 1354

Identifier Type: -

Identifier Source: org_study_id

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