LTA Pilot Study of Glucarpidase in Patients With Central Nervous System Lymphoma
- Conditions
- Central Nervous System Lymphoma
- Registration Number
- NCT03684980
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 64
Inclusion Criteria:<br><br>Arm A:<br><br> - Histologically documented B-cell non-Hodgkins lymphoma involving the brain, spinal<br> cord, and/or leptomeningeal space.<br><br> °Patients in whom the type of lymphoma could not be determined or is unknown (e.g.,<br> not enough tissue for further analysis) are assumed to have a B cell lymphoma and<br> are eligible<br><br> - Patients with parenchymal lesions must have received no more than two cycles of<br> treatment for treatment of CNS lymphoma or have unequivocal evidence of disease<br> progression on imaging (MRI of the brain/spine or CT head) 28 days prior to study<br> registration. For patients with leptomeningeal disease only, CSF cytology must<br> document lymphoma cells and/or imaging findings must be consistent with CSF disease<br> 28 days prior to study registration (at the discretion of the investigator).<br><br> - Patients who have already received two doses of treatment of CNS lymphoma are<br> eligible for enrollment.<br><br> - (Arm A only) as long as they are planned for at least 6 additional doses of<br> methotrexate. Patients must not have evidence of systemic non-Hodgkin lymphoma<br> requiring active treatment.<br><br> - Men and woman must be at least 18 years of age on the day of consenting to the<br> study.<br><br> - Patients must have a Karnofsky Performance Status (KPS) = 50 (See Appendix 2).<br><br> - Patients must be willing and able to comply with scheduled visits, treatment plan,<br> and laboratory tests.<br><br> - Patients must have adequate bone marrow and organ function shown by:<br><br> - Absolute neutrophil count (ANC) = 1.0 x 10^9/L;<br><br> - Platelets = 100 x 10^9/L and no platelet transfusion within the past 28 days<br> prior to study registration;<br><br> - Hemoglobin (Hgb) = 8 g/dL and no red blood cells (RBC) transfusion within the<br> past 28 days prior to study registration;<br><br> - International Normalized Ratio (INR) = 1.5 and PTT (aPTT) = 1.5 times the upper<br> limit of normal;<br><br> - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 times<br> the upper limit of normal;<br><br> - Serum bilirubin = 1.5 times the upper limit of normal; or total bilirubin = 3<br> times the upper limit of normal with direct bilirubin within the normal range<br> in patients with well documented Gilbert Syndrome;<br><br> - CrCl = 60 mL/min using the Cockcroft-Gault equation. Men: CrCl (min/mL) =<br> (140-age) X (actual weight in kg) / 72 X serum creatinine (mg/dL) Women: CrCl<br> (mL/min) = (140-age) X (actual weight in kg) X 0.85 / 72 X serum creatinine<br> (mg/dL)<br><br> - Women of reproductive potential must agree to use highly effective methods of birth<br> control during the period of therapy and for 30 days after the last dose of the<br> study drug. Men who are sexually active must agree to use highly effective<br> contraception during the period of therapy and for 3 months after the last dose.<br><br> - Female subjects of childbearing potential must have a negative plasma pregnancy test<br> upon study entry.<br><br> - Patients must be able to tolerate MRI/CT scans.<br><br> - Patients must be able to tolerate lumbar puncture and/or Ommaya taps.<br><br> - Participants must have recovered to grade 1 toxicity from prior therapy. NOTE:<br> Patients who have initiated and received up to two cycles of treatment will NOT be<br> excluded from study Arm A as long as all pretreatment assessments have been<br> completed within 28 days of trial initiation.<br><br>Arms B and D:<br><br> - Histologically documented B-cell non-Hodgkin's lymphoma involving the brain, spinal<br> cord, and/or leptomeningeal space<br><br> ° Patients in whom the type of lymphoma could not be determined or is unknown (e.g.,<br> not enough tissue for further analysis) are assumed to have a B cell lymphoma and<br> are eligible<br><br> - Patients must be treatment naïve or have unequivocal evidence of disease progression<br> on imaging (MRI of the brain/spine or CT head) 28 days prior to initiation of MTX.<br> For patients with leptomeningeal disease only, CSF cytology must document lymphoma<br> cells and/or imaging findings must be consistent with CSF disease 28 days prior to<br> initiation of MTX. (at the discretion of the investigator)<br><br> - Patients must not have evidence of systemic non-Hodgkin lymphoma requiring active<br> treatment<br><br> - Men and woman must be at least 18 years of age on the day of consenting to the study<br><br> - Patients must have a Karnofsky Performance Status (KPS) >/= 70 or >/= 50 if KPS is<br> due to a neurologic deficit attributed to active disease<br><br> - Patients must be willing and able to comply with scheduled visits, treatment plan,<br> and laboratory tests<br><br> - Patients must have adequate bone marrow and organ function shown by:<br><br> - Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L<br><br> - Platelets >/= 100 x 10^9/L and no platelet transfusion within the past 28 days<br> prior to study registration<br><br> - Hemoglobin (Hgb) >/= 8g/dL and no red blood cells (RBC) transfusion within the<br> past 28 days prior to study registration<br><br> - International Normalized Ratio (INR) </= 1.5 and PTT (aPTT) </= 1.5 times the<br> upper limit of normal<br><br> - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) </= 3 times<br> the upper limit of normal<br><br> - Serum bilirubin </= 1.5 times the upper limit of normal; or total bilirubin </=<br> 3 times the upper limit of normal with direct bilirubin within the normal range<br> in patients with well documented Gilbert Syndrome<br><br> - CrCl >/= 60 mL/min using the Cockcroft-Gault equation Men: CrCl (min/mL) =<br> (140-age) X (actual weight in kg) / 72 X serum creatinine (mg/dL) Women: CrCl<br> (mL/min) = (140-age) X (actual weight in kg) X 0.85 / 72 X serum creatinine<br> (mg/dL)<br><br> - Women of reproductive potential must agree to use highly effective methods of birth<br> control during the period of therapy and for 30 days after the last dose of the<br> study drug. Men who are sexually active must agree to use highly effective<br> contraception during the period of therapy and for 3 months after the last dose.<br><br> - Female subjects of childbearing potential must have a negative plasma pregnancy test<br> upon study entry<br><br> - Patients must be able to tolerate MRI/CT scans<br><br> - Patients must be able to tolerate lumbar puncture and/or Ommaya taps<br><br> - Participants must have recovered to grade 1 toxicity from prior therapy<br><br> - Patients with ocular manifestation of systemic lymphoma are allowed if repeat<br> ophthalmologic exam is planned for the end of therapy. If ocular disease remains<br> present, ocular-directed therapy may be administered after treatment with<br> methotrexate.<br><br> - Patients must be able to tolerate po hydration (Arm D only)<br><br>NOTE: Prior autologous stem cell transplant as well as prior radiation to the CNS does<br>NOT prevent patients from enrollment into the trial.<br><br>Arm Outpatient MTX Therapy in times of COVID-19:<br><br> - Patients eligible for inclusion in this arm must be eligible for inpatient MTX<br> administration for treatment of CNS lymphoma. Patients should have received prior<br> MTX therapy without major adverse events.<br><br> - Female subjects of childbearing potential must h
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method number of patients that have significant reduction of serum methotrexate levels
- Secondary Outcome Measures
Name Time Method