AzTrials
AzTrials

Central Nervous System LymphomaEarly Phase 1NCT03684980

LTA Pilot Study of Glucarpidase in Patients With Central Nervous System Lymphoma

A Early Phase 1 study testing Methotrexate, Rituximab and leucovorin in people with Central Nervous System Lymphoma, run by Memorial Sloan Kettering Cancer Center at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The purpose of this study is to test the effects of a drug called Voraxaze when it's routinely given in combination with methotrexate and rituximab, the standard treatment for CNSL. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Central Nervous System Lymphoma
What is being tested?
Methotrexate, Rituximab and leucovorin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
11 sitesUnited States
Study dates
14 Nov 2018to Nov 2027
Phase
Early Phase 1
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Arm A:
  • Histologically documented B-cell non-Hodgkin"s lymphoma involving the brain, spinal cord, and/or leptomeningeal space.
  • °Patients in whom the type of lymphoma could not be determined or is unknown (e.g., not enough tissue for further analysis) are assumed to have a B cell lymphoma and are eligible
  • Patients with parenchymal lesions must have received no more than two cycles of treatment for treatment of CNS lymphoma or have unequivocal evidence of disease progression on imaging (MRI of the brain/spine or CT head) 28 days prior to study registration. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings must be consistent with CSF disease 28 days prior to study registration (at the discretion of the investigator).
  • Patients who have already received two doses of treatment of CNS lymphoma are eligible for enrollment.
  • (Arm A only) as long as they are planned for at least 6 additional doses of methotrexate. Patients must not have evidence of systemic non-Hodgkin lymphoma requiring active treatment.
Show all 57Show fewer
  • Men and woman must be at least 18 years of age on the day of consenting to the study.
  • Patients must have a Karnofsky Performance Status (KPS) ≥ 50 (See Appendix 2).
  • Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
  • Patients must have adequate bone marrow and organ function shown by:
  • 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) ≥ 8 g/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 ≥ 60 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)
  • 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.
  • Patients must be able to tolerate MRI/CT scans.
  • Patients must be able to tolerate lumbar puncture and/or Ommaya taps.
  • Participants must have recovered to grade 1 toxicity from prior therapy. NOTE: Patients who have initiated and received up to two cycles of treatment will NOT be excluded from study Arm A as long as all pretreatment assessments have been completed within 28 days of trial initiation.
  • Arms B and D:
  • Histologically documented B-cell non-Hodgkin's lymphoma involving the brain, spinal cord, and/or leptomeningeal space
  • ° Patients in whom the type of lymphoma could not be determined or is unknown (e.g., not enough tissue for further analysis) are assumed to have a B cell lymphoma and are eligible
  • Patients must be treatment naïve or have unequivocal evidence of disease progression on imaging (MRI of the brain/spine or CT head) 28 days prior to initiation of MTX. For patients with leptomeningeal disease only, CSF cytology must document lymphoma cells and/or imaging findings must be consistent with CSF disease 28 days prior to initiation of MTX. (at the discretion of the investigator)
  • Patients must not have evidence of systemic non-Hodgkin lymphoma requiring active treatment
  • Men and woman must be at least 18 years of age on the day of consenting to the study
  • Patients must have a Karnofsky Performance Status (KPS) >/= 70 or >/= 50 if KPS is due to a neurologic deficit attributed to active disease
  • Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests
  • Patients must have adequate bone marrow and organ function shown by:
  • 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 >/= 60 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)
  • 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
  • Patients must be able to tolerate MRI/CT scans
  • Patients must be able to tolerate lumbar puncture and/or Ommaya taps
  • Participants must have recovered to grade 1 toxicity from prior therapy
  • Patients with ocular manifestation of systemic lymphoma are allowed if repeat ophthalmologic exam is planned for the end of therapy. If ocular disease remains present, ocular-directed therapy may be administered after treatment with methotrexate.
  • Patients must be able to tolerate po hydration (Arm D only)
  • NOTE: Prior autologous stem cell transplant as well as prior radiation to the CNS does NOT prevent patients from enrollment into the trial.
  • Arm Outpatient MTX Therapy in times of COVID-19:
  • Patients eligible for inclusion in this arm must be eligible for inpatient MTX administration for treatment of CNS lymphoma. Patients should have received prior MTX therapy without major adverse events.
  • Female subjects of childbearing potential must have a negative plasma pregnancy test upon study entry.
  • Arm E:
  • Documented history of CNS lymphoma, appropriate for standard of care inpatient MTX administration as determined by their treating physician
  • Men and woman must be at least 18 years of age on the day of consenting to the study.
  • Patients must be willing and able to comply with scheduled visits, treatment plan, and laboratory tests.
  • Patients must meet at least ONE of the following additional criteria
  • MTX >100 nmol/L ≥ 72 hours after initiation of MTX
  • History of prolonged MTX clearance (≥ 72 hours) after prior MTX administration of equal or higher dose (g/m2)
  • CrCl < 60 ml/min calculated by Cockroft-Gault equation oHistory of MTX-related toxicity, CTCAE v5 grade 2 or higher (must have recovered to a grade 1 toxicity)

Who cannot join

  • Arms A, B and D:
  • Patient with SCNSL requiring treatment for extra-CNS disease are excluded.
  • Patient concurrently using other approved or investigational antineoplastic agents.
  • Patient has received chemotherapy, monoclonal antibodies or targeted anticancer therapy ≤ 4 weeks or 5 half-lives, whichever is shorter, or 6 weeks for nitrosoureas or mitomycin-C prior to starting the study drug, or the patient has not recovered from the side effects of such therapy. Exceptions are allowed for rituximab and methotrexate for patients enrolling Arm A as long as patients have recovered from side effects.
  • Patient has received external beam radiation therapy to the CNS within 28 days of the first dose of the study drug.
  • Patient has an active concurrent malignancy requiring active therapy.
Show all 41Show fewer
  • The patient has been treated with radio- or toxin-immunoconjugates within 70 days of the first dose of the study drug.
  • Patient weighs <40kg
  • Patient is allergic to components of the study drug.
  • Patient is known to have human immunodeficiency virus (HIV) infection.
  • Patient is known to have a history of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) as determined by serologic tests.
  • Severe, active medical co-morbidity such as unstable angina and/or congestive heart failure, coronary artery disease, significant abnormalities on electrocardiogram (EKG), uncontrolled or symptomatic arrhythmias or valvular disease; active infection, severe chronic obstructive pulmonary disease or other respiratory illness, hepatic insufficiency, known pre-existing immunodeficiency as seen in organ transplant recipients, renal failure with CrCl <60 mL/min.
  • Patient has a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject"s safety or put the study outcomes at undue risk.
  • Patient has large pleural or ascetic fluid collection.
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
  • Prior severe allergic reaction to any of the study drugs that cannot be resolved with medication.
  • Patient has undergone prior allogenic stem cell transplant (autologous stem cell transplant is NOT an exclusion).
  • Arm Outpatient MTX Therapy in times of COVID-19:
  • Patients eligible for this arm must not meet any of the following criteria:
  • Patients with SCNSL requiring treatment for extra-CNS disease are excluded.
  • Patients weighing <40kg
  • Inadequate bone marrow and organ function shown by:
  • Absolute neutrophil count (ANC) </= 0.5 x 10^9/L
  • Platelets </= 75 x 10^9/L
  • Hemoglobin (Hgb) </= 8 g/dL
  • 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 outside of the normal range in patients with well documented Gilbert Syndrome
  • Creatinine >/= 1.3 mg/dL
  • Patients allergic to components of the study drug.
  • Patients with severe, active medical co-morbidity such as unstable angina and/or congestive heart failure, coronary artery disease, significant abnormalities on electrocardiogram (EKG), uncontrolled or symptomatic arrhythmias or valvular disease; active infection, severe chronic obstructive pulmonary disease or other respiratory illness, hepatic insufficiency, known pre-existing immunodeficiency as seen in organ transplant recipients, renal failure with creatinine >/= 1.3 mg/dL.
  • Patients with a life-threatening illness, medical condition, or organ system dysfunction that, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk
  • Patients with large pleural or ascetic fluid collection
  • Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic. 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
  • Arm E:
  • Patients eligible for this arm must not meet any of the following criteria:
  • Weight <40kg
  • Prior severe allergic reaction to methotrexate or glucarpidase that cannot be resolved withmedication.
  • Severe, active medical co-morbidity such as unstable angina and/or congestive heart failure, coronary artery disease, significant abnormalities on electrocardiogram (EKG), uncontrolled or symptomatic arrhythmias or valvular disease; active uncontrolled infection, severe chronic obstructive pulmonary disease or other respiratory illness, hepatic insufficiency
  • Patient has a life-threatening illness, medical condition, or organ system dysfunctionthat, in the opinion of the investigator, could compromise the subject's safety or put the study outcomes at undue risk.
  • Presence of large pleural or ascetic fluid collection.
  • Treatment with MTX dose greater than 8 g/m2

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana Farber Cancer Institute (Data Collection and Specimen Analysis)

    Boston, Massachusetts, 02115

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Cleveland Clinic (Data Collection and Specimen Collection)

    Cleveland, Ohio, 44195

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Memorial Sloan Kettering Monmouth

    Middletown, New Jersey, 07748

  • Memorial Sloan Kettering Bergen

    Montvale, New Jersey, 07645

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

Other trials in United States

About this study

The purpose of this study is to test the effects of a drug called Voraxaze when it's routinely given in combination with methotrexate and rituximab, the standard treatment for CNSL.

Being tested
Methotrexate, Rituximab, leucovorin, Glucarpidase
Keywords
Voraxaze (glucarpidase), B-cell non-Hodgkin"s lymphoma involving the brain, B-cell non-Hodgkin"s lymphoma involving spinal cord, and/or leptomeningeal space

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MethotrexateDrug

    (Cohort A) will receive MTX 3 g/m2 or (Cohort B) will receive MTX 8 g/m^2 (Cohort E) will receive MTX ≤ 3.5 g/ m2

  • RituximabDrug

    Patients will be treated with rituximab 500 mg/m^2.

  • leucovorinDrug

    Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.

  • GlucarpidaseDrug

    Also called Voraxaze

    Glucarpidase 2000 units. Arm E 1000 units.

Study groups in NCT03684980
Study groupRoleWhat they receive
Arm A - Rituximab + MTX + GlucarpidaseExperimentalPatients will receive rituximab Day 1 (+/- 7 days) and MTX Day 2 (+/- 7 days) as per standard of care. Voraxaze will be administered each cycle 24 hours (+/- 2 h) after start of MTX infusion. Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8. Patients will be treated with rituximab 500 mg/m^2. (Cohort A) will receive MTX 3 g/m2. Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.
Receives: Drug: Methotrexate; Drug: Rituximab; Drug: leucovorin; Drug: Glucarpidase
Arm B - Rituximab + MTX + GlucarpidaseExperimentalPatients will receive up to 8 cycles of treatment consisting of rituximab Day 1 (+/- 7 days) and MTX Day 2 (+/- 7 days) as per standard of care. Voraxaze will be administered each cycle 24 hours (+/- 2 h) after start of MTX infusion. Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8. Patients will be treated with rituximab 500 mg/m^2. (Cohort B) will receive MTX 8 g/m2. Patients will also receive standard of care leucovorin rescue starting at least 24 hours after MTX and 2 hours after Voraxaze. Cycles will be 14 days long.
Receives: Drug: Rituximab; Drug: Glucarpidase
Arm C - HD-MTX (Arm Outpatient MTX Therapy in times of COVID-19)ExperimentalMTX ≤ 3.5 g/m2 will be administered on Day 1, along with pre- and post- hydration. Patients will return on Day 2 for continued hydration and glucarpidase 2000 units. Glucarpidase rapidly and sustainably reduces serum MTX levels >95% without crossing the blood brain barrier, effectively resulting in systemic MTX clearance. Patients will return for bloodwork on Day 3 to document MTX clearance. Arm Outpatient MTX Therapy in times of COVID-19 will only be a single-institution arm, only open at Memorial Sloan Kettering Cancer Center.
Receives: Drug: Methotrexate; Drug: Glucarpidase
Arm D -Rituximab + MTX + GlucarpidaseExperimentalUp to 12 patients will be included in Arm D of this study. Cycles will be 14 days long. All patients will receive MTX 3.5 g/m2 administered Day 1 of each cycle (+/- 7 days, a minimum of 14 days required between doses). Glucarpidase will be administered 24 hours (+/- 2 hr) after start of MTX infusion except in cycles 1-2 of Cohort B. Dose of glucarpidase will be 2000 units in Cohort A (first 4 patients) and 1000 units in Cohort B (remaining 8 patients). Patients in Arm D will receive 8 cycles of treatment. Cycles 1 and 2 will be administered in patient while Cycles 3-8 may be in the outpatient setting. Concurrent chemotherapy such as vincristine, procarbazine, and/or ibrutinib may be administered at the investigator's discretion and in accordance with standard of care. In Cohort B, all cycles will be administered with rituximab 500 mg/m2. Rituximab should be administered prior to glucarpidase (window -4 days).
Receives: Drug: Methotrexate; Drug: Rituximab; Drug: Glucarpidase
Arm E-glucarpidase 1000u + MTXExperimentalStudy treatment consists of glucarpidase 1000u, to be administered at least 24 hours after start of standard of care MTX. Patients will have a standard of care methotrexate level drawn within 6 hours of planned glucarpidase administration to confirm eligibility (must reflect MTX > 100 nmol/L)
Receives: Drug: Methotrexate; Drug: Glucarpidase

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. number of patients that have significant reduction of serum methotrexate levels

    All serum samples will be tested via MTX immunoassay (measures MTX levels in addition to byproducts) as well as HPLC or mass spectroscopy which will reveal plasma concentrations of MTX and DAMPA separately.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2018
  2. Study start14 Nov 2018
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
This is an open-label, non-randomized, pilot study of Voraxaze administered following standard of care MTX and rituximab in patients with CNS lymphoma.
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03684980
Sponsor's protocol ID
18-410
Status last verified
Apr 2026
First submitted
24 Sep 2018
Last updated
15 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Schaff LR, Carlow D, Schofield R, Wongchai V, Madzsar J, Hyde A, Reiner AS, Panageas KS, DeAngelis LM, Mellinghoff IK, Lobbous M, Nabors LB, Grommes C. Low-Dose Planned Glucarpidase Allows Safe Outpatient High-Dose Methotrexate Treatment for CNS Lymphoma. JCO Oncol Pract. 2024 Oct;20(10):1384-1390. doi: 10.1200/OP.24.00080. Epub 2024 Jun 25.

    PubMed 38917404

  • Schaff LR, Lobbous M, Carlow D, Schofield R, Gavrilovic IT, Miller AM, Stone JB, Piotrowski AF, Sener U, Skakodub A, Acosta EP, Ryan KJ, Mellinghoff IK, DeAngelis LM, Nabors LB, Grommes C. Routine use of low-dose glucarpidase following high-dose methotrexate in adult patients with CNS lymphoma: an open-label, multi-center phase I study. BMC Cancer. 2022 Jan 13;22(1):60. doi: 10.1186/s12885-021-09164-x.

    PubMed 35027038

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Methotrexate, Rituximab and leucovorin in people with Central Nervous System Lymphoma, run by Memorial Sloan Kettering Cancer Center at 11 sites 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 57 inclusion and 41 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: under way, not looking for participants, as of the sponsor's last update on 15 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

number of patients that have significant reduction of serum methotrexate levels (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03684980, which also lists 2 linked publications.

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 15 Apr 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in