HM-178: Assessing Methods for Improvement in Methotrexate Toxicity Management and Detection of Central Nervous System Involvement of Aggressive Lymphoma

NCT04668768 | Suspended Phase 2 DMC FDA Drug

• 2 other identifiers: HM-17820-1071
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to use glucarpidase prophylactically to treat methotrexate induced toxicities in lymphoma patients with cerebral involvement.

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Rate of methotrexate clearance

  Number days for methotrexate clearance

  6 months

Secondary Outcomes (1)

• Progression free survival

  6 months

Study Arms (1)

Glucarpidase

EXPERIMENTAL

Prophylactic glucarpidase treatment

Drug: Glucarpidase

Interventions

Glucarpidase DRUG

Glucarpidase injection to prevent toxicities due to high dose methotrexate treatment

Glucarpidase

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed diagnosis of Non-Hodgkin Lymphoma and either:
• High risk of CNS relapse warranting MTX prophylaxis
• Evidence of CNS involvement (either PCNSL or secondary CNS lymphoma) warranting therapeutic MTX treatment
• DLBCL
• i. Transformation to DLBCL from an antecedent low-grade lymphoma is permitted d. Burkitt lymphoma (BL) e. Plasmablastic lymphoma f. Blastoid variant of Mantle Cell lymphoma g. Richter Transformation h. Primary CNS Lymphoma i. Secondary CNS lymphoma of any B cell lineage j. B cell Non-Hodgkin Lymphoma with neurologic symptoms suspicious for CNS involvement
• Patients must have at least one of the following 2 criteria;
• aged \> 65 year with baseline CrCl (creatinine clearance) \> 30 ml/min/1.73 m2
• any age with a baseline CrCl of 30-59 ml/min/1.73 m2
• Patients must meet criteria for and are appropriate candidates for treatment or prophylaxis with high dose systemic MTX of 3.5 g/m2 if CrCl \> 60 ml/min and 2 g/m2 if Cr 30-59 mL/min.
• Patients planned to have 2 or more cycles of high dose MTX as part of treatment regimen. If patents are planned to have more than 4 cycles of MTX, they can be included in study, however glucarpidase will be provided only for up to 4 cycles of MTX.
• Patients must be willing and eligible to undergo diagnostic lumbar puncture for initial staging and also post treatment if evidence of CNS involvement
• Patients with confirmed CNS involvement of disease on lumbar puncture testing or those with clinical symptoms of CNS involvement will require baseline and post treatment brain and spinal MRI. If there is contraindication to MRI, CT scan is permitted.
• Patients must be willing and able to comply with scheduled visits and testing
• Patients must have adequate bone marrow and organ function
• Absolute neutrophil count (ANC) \>/= 1.0 x 10\^9/L

You may not qualify if:

• Patients who received CNS directed therapy (intrathecal chemotherapy or systemic HD-MTX) or glucarpidase prior to enrollment. Patients may receive intrathecal prophylaxis at time of initial CSF (cerebrospinal) fluid collection or as part of treatment protocol
• Patients with moderate or severe pleural effusion and/or abdominal ascites at time of enrollment that are not amenable to therapeutic thoracentesis or paracentesis, respectively
• Patients with contraindication or refusal to have cerebrospinal fluid sampling
• Patients with contraindication or refusal to have inpatient HD-MTX administration as part of therapy Patients may not be receiving any other investigational agent
• Patients who will require any medications or substances that are inhibitors or inducers of glucarpidase or MTX during hospitalization for therapy administration are ineligible.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

glucarpidase

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 16, 2020
• Study Start: April 16, 2021
• Primary Completion: December 1, 2024
• Study Completion: April 1, 2025
• Last Updated: March 22, 2024

Record last verified: 2024-03

Locations

US (1)