LymphomaPhase 2NCT04668768
HM-178: Assessing Methods for Improvement in Methotrexate Toxicity Management and Detection of Central Nervous System Involvement of Aggressive Lymphoma
A Phase 2 study testing Glucarpidase in people with Lymphoma, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This is a study to use glucarpidase prophylactically to treat methotrexate induced toxicities in lymphoma patients with cerebral involvement. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- Glucarpidase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2021to Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
- 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;
Show all 24Show fewer
- 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
- Platelets >/= 100 x 10^9/L and no platelet transfusion within the past 28 days prior to study registration
- Hemoglobin (Hgb) >/= 8g/dL and no red blood cells (RBC) transfusion within the past 28 days prior to study registration
- International Normalized Ratio (INR) </= 1.5 and PTT (aPTT) </= 1.5 times the upper limit of normal
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 3 times the upper limit of normal
- Serum bilirubin </= 1.5 times the upper limit of normal; or total bilirubin </= 3 times the upper limit of normal with direct bilirubin within the normal range in patients with well documented Gilbert Syndrome
- CrCl >/= 30 mL/min using the Cockcroft-Gault equation; Men: CrCl (min/mL) = (140-age) X (actual weight in kg) / 72 X serum creatinine (mg/dL); Women: CrCl (mL/min) = (140-age) X (actual weight in kg) X 0.85 / 72 X serum creatinine (mg/dL)
- Patients with therapeutically intervenable ascites fluid and/or pleural effusions are permitted on trial. However, patients must demonstrate absent or mild/trace effusion on post procedure imaging with ultrasound or CT scan within 7 days of each MTX cycle
- Women of reproductive potential must agree to use highly effective methods of birth control during the period of therapy and for 30 days after the last dose of the study drug. Men who are sexually active must agree to use highly effective contraception during the period of therapy and for 3 months after the last dose.
- Female subjects of childbearing potential must have a negative plasma pregnancy test upon study entry
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
About this study
This is a study to use glucarpidase prophylactically to treat methotrexate induced toxicities in lymphoma patients with cerebral involvement.
Read the detailed description
Treatment and prophylaxis against CNS (central nervous system) lymphoma typically consist of a regimen containing high dose methotrexate (HD MTX), which requires inpatient monitoring in order to ensure adequate clearance of methotrexate levels (MTX). The goal of this prospective, multi-institution study is to evaluate the effect of prophylactic glucarpidase in patients receiving high dose MTX and are at increased risk of delayed MTX clearance and nephrotoxicity. Glucarpidase is a recombinant bacterial enzyme (carboxypeptidase G2) that can convert MTX to non-cytotoxic metabolites (DAMPA). This is the first controlled trial comparing glucarpidase with supportive care alone in patients with MTX induced nephrotoxicity and delayed MTX clearance.
- Conditions
- Lymphoma
- Being tested
- Glucarpidase
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucarpidaseDrug
Glucarpidase injection to prevent toxicities due to high dose methotrexate treatment
| Study group | Role | What they receive |
|---|---|---|
| Glucarpidase | Experimental | Prophylactic glucarpidase treatment Receives: Drug: Glucarpidase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of methotrexate clearance
Number days for methotrexate clearance
Measured: 6 months
Secondary outcomes (1)
Progression free survival
Duration that patients is free of cancer from the time of treatment
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2020
- Study start16 Apr 2021
- Primary completionDec 2024 (estimated)
- Study completionApr 2025 (estimated)
Why it stopped: To be terminated due to slow accrual, patient still in follow up
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04668768
- Sponsor's protocol ID
- HM-178
- Other IDs
- 20-1071
- Status last verified
- Mar 2024
- First submitted
- 9 Dec 2020
- Last updated
- 22 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HM-178: Assessing Methods for Improvement in Methotrexate Toxicity Management and Detection of Central Nervous System Involvement of Aggressive Lymphoma
- ClinicalTrials.gov ID
- NCT04668768
- Acronym / sponsor ID
- HM-178
- Conditions
- Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: To be terminated due to slow accrual, patient still in follow up
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 16 Apr 2021 (actual)
- Primary completion
- Dec 2024 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 16 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to use glucarpidase prophylactically to treat methotrexate induced toxicities in lymphoma patients with cerebral involvement.
Detailed description
Treatment and prophylaxis against CNS (central nervous system) lymphoma typically consist of a regimen containing high dose methotrexate (HD MTX), which requires inpatient monitoring in order to ensure adequate clearance of methotrexate levels (MTX). The goal of this prospective, multi-institution study is to evaluate the effect of prophylactic glucarpidase in patients receiving high dose MTX and are at increased risk of delayed MTX clearance and nephrotoxicity. Glucarpidase is a recombinant bacterial enzyme (carboxypeptidase G2) that can convert MTX to non-cytotoxic metabolites (DAMPA). This is the first controlled trial comparing glucarpidase with supportive care alone in patients with MTX induced nephrotoxicity and delayed MTX clearance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Glucarpidase | Experimental | Drug: GlucarpidaseProphylactic glucarpidase treatment |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (24 listed)
- Patients must have histologically or cytologically confirmed diagnosis of Non-Hodgkin Lymphoma and either:
- Patients must have at least one of the following 2 criteria;
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlucarpidaseGlucarpidase injection to prevent toxicities due to high dose methotrexate treatment | Drug | Glucarpidase |
Primary outcome
Rate of methotrexate clearance
Time frame: 6 months
Number days for methotrexate clearance
1 secondary outcome
Progression free survival
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Glucarpidase in people with Lymphoma, run by Fox Chase Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of methotrexate clearance (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.