Non Hodgkin Lymphoma Clinical Trial

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

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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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.
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) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) Serum bilirubin 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.

Exclusion Criteria:

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.
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 mLmin.
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) Platelets Hemoglobin (Hgb) 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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Early Phase 1

Estimated Enrollment:

44

Study ID:

NCT03684980

Recruitment Status:

Recruiting

Sponsor:

Memorial Sloan Kettering Cancer Center

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There are 10 Locations for this study

See Locations Near You

University of Alabama at Birmingham
Birmingham Alabama, 35294, United States More Info
Burt Nabors, MD
Contact
205-934-1432
Burt Nabors, MD
Principal Investigator
Dana Farber Cancer Institute (Data Collection and Specimen Analysis)
Boston Massachusetts, 02115, United States More Info
Lakshmi Nayak, MD
Contact
617-632-2166
Memoral Sloan Kettering Basking Ridge
Basking Ridge New Jersey, 07920, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Christian Grommes
Contact
212-639-4058
Memorial Sloan Kettering Monmouth
Middletown New Jersey, 07748, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Memorial Sloan Kettering Bergen
Montvale New Jersey, 07645, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Memorial Sloan Kettering Commack
Commack New York, 11725, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Memorial Sloan Kettering Westchester
Harrison New York, 10604, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Memorial Sloan Kettering Cancer Center
New York New York, 10065, United States More Info
Lauren Schaff, MD
Contact
Christian Grommes, MD
Contact
212-639-4058
Memorial Sloan Kettering Nassau
Uniondale New York, 11553, United States More Info
Lauren Schaff, MD
Contact
212-610-0485
Cleveland Clinic (Data Collection and Specimen Collection)
Cleveland Ohio, 44195, United States More Info
Mina Loubbos, MD
Contact
216-445-3307

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Early Phase 1

Estimated Enrollment:

44

Study ID:

NCT03684980

Recruitment Status:

Recruiting

Sponsor:


Memorial Sloan Kettering Cancer Center

How clear is this clinincal trial information?

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