## Protocol Section
### Identification Module
**NCT ID:** NCT05519579

**Brief Title:** Intrathecal Chemoprophylaxis to Prevent Neurotoxicity Associated With Blinatumomab Therapy for Acute Lymphoblastic Leukemia

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

#### Organization Study ID Info
**ID:** NSH 1354
#### Organization
**Class:** OTHER
**Full Name:** Northside Hospital, Inc.
### Status Module
#### Completion Date
**Date:** 2025-08-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-04-15

**Type:** ACTUAL

**Last Update Submit Date:** 2024-04-12

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-11-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-06-30

**Type:** ACTUAL

**Status Verified Date:** 2024-04

#### Study First Post Date
**Date:** 2022-08-29
**Type:** ACTUAL
**Study First Submit Date:** 2022-08-25
**Study First Submit QC Date:** 2022-08-25
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Northside Hospital, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Is US Export:** True

### Description Module

**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 Module

**Conditions:**

- Acute Lymphoblastic Leukemia

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: Methotrexate

- Drug: Blinatumomab

**Label:** Intrathecal chemotherapy before blinatumomab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intrathecal chemotherapy before blinatumomab

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

**Name:** Methotrexate

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Intrathecal chemotherapy before blinatumomab

**Description:** Blinatumomab 28ug/day continuous infusion for 4 weeks

**Name:** Blinatumomab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Record occurrence and severity of neurotoxicity based on CTCAE criteria

**Measure:** Number of participants that experienced neurotoxicity during the first cycle of blinatumomab therapy

**Time Frame:** 28 days after first infusion

#### Secondary Outcomes

**Description:** Record occurrence and severity of cytokine release syndrome based on CTCAE criteria

**Measure:** Number of participants that experienced cytokine release syndrome during the first cycle of blinatumomab therapy

**Time Frame:** 28 days after first infusion

**Description:** Conduct disease restaging assessments, such as bone marrow biopsies and lumbar punctures, to determine response to treatment

**Measure:** 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 Module

**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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** caitlin.guzowski@northside.com

**Name:** Caitlin Guzowski

**Phone:** 404-851-8523

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Atlanta

**Contacts:**

***Contact 1:***

- **Email:** caitlin.guzowski@northside.com

- **Name:** Caitlin Guzowski, MBA, MHA

- **Phone:** 404-851-8523

- **Role:** CONTACT

***Contact 2:***

- **Name:** H. Kent Holland, MD

- **Role:** SUB_INVESTIGATOR

***Contact 3:***

- **Name:** Asad Bashey, MD

- **Role:** SUB_INVESTIGATOR

***Contact 4:***

- **Name:** Lawrence E Morris, MD

- **Role:** SUB_INVESTIGATOR

***Contact 5:***

- **Name:** Scott Solomon, MD

- **Role:** SUB_INVESTIGATOR

***Contact 6:***

- **Name:** Melhem Solh, MD

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 7:***

- **Name:** Lizamarie Bachier-Rodriguez, MD

- **Role:** SUB_INVESTIGATOR

**Country:** United States

**Facility:** Northside Hospital

**State:** Georgia

**Status:** RECRUITING

**Zip:** 30342

#### Overall Officials

**Official 1:**

**Affiliation:** Blood and Marrow Transplant Group of Georgia

**Name:** Melhem Solh, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** 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

**Citation:** 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. Erratum In: Blood. 2019 Jun 13;133(24):2625.

**PMID:** 29358182

**Citation:** 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

**Citation:** 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. Erratum In: Lancet Oncol. 2015 Apr;16(4):e158.

**PMID:** 25524800

**Citation:** 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

**Citation:** 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

**Citation:** 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. Erratum In: J Clin Oncol. 2017 Aug 10;35(23):2722. J Clin Oncol. 2017 Aug 20;35(24):2856.

**PMID:** 28355115

**Citation:** 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

**Citation:** 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

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000008206

- Term: Lymphatic Diseases

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000011041

- Term: Poisoning

- ID: D000064419

- Term: Chemically-Induced Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC25

- Name: Substance Related Disorders

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: HIGH

- As Found: Lymphoblastic Leukemia

- ID: M27585

- Name: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: M22080

- Name: Neurotoxicity Syndromes

- Relevance: HIGH

- As Found: Neurotoxicity

- ID: M11220

- Name: Lymphoma

- Relevance: LOW

- As Found: Unknown

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13931

- Name: Poisoning

- Relevance: LOW

- As Found: Unknown

- ID: M30302

- Name: Chemically-Induced Disorders

- Relevance: LOW

- As Found: Unknown

- ID: T175

- Name: Acute Lymphoblastic Leukemia

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: T3533

- Name: Lymphoblastic Lymphoma

- Relevance: HIGH

- As Found: Acute Lymphoblastic Leukemia

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

- ID: T4120

- Name: Neurotoxicity Syndromes

- Relevance: HIGH

- As Found: Neurotoxicity

- ID: T3543

- Name: Lymphosarcoma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000054198

- Term: Precursor Cell Lymphoblastic Leukemia-Lymphoma

- ID: D000007945

- Term: Leukemia, Lymphoid

- ID: D000020258

- Term: Neurotoxicity Syndromes

### Intervention Browse Module - Ancestors

- ID: D000000020

- Term: Abortifacient Agents, Nonsteroidal

- ID: D000000019

- Term: Abortifacient Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000003879

- Term: Dermatologic Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000005493

- Term: Folic Acid Antagonists

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M11703

- Name: Methotrexate

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M287547

- Name: Blinatumomab

- Relevance: HIGH

- As Found: Inguinal Hernia

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M7074

- Name: Dermatologic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M8619

- Name: Folic Acid Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008727

- Term: Methotrexate

- ID: C000510808

- Term: Blinatumomab

### Misc Info Module

- Version Holder: 2024-05-24
