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Trial record 5 of 48 for:    "Central Nervous System Lymphoma" | "Vitamin B9"

Study of Voraxaze in Patients With Central Nervous System Lymphoma

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ClinicalTrials.gov Identifier: NCT03684980
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : April 8, 2019
Sponsor:
Collaborator:
University of Alabama at Birmingham
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Central Nervous System Lymphoma Drug: Voraxaze Drug: Methotrexate Drug: Rituximab Drug: leucovorin Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Pilot Study of Voraxaze (Glucarpidase) in Patients With Central Nervous System Lymphoma
Actual Study Start Date : November 14, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: MTX 3 g/m^2
Patients 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 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.
Drug: Voraxaze
Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8.

Drug: Methotrexate
(Cohort A) will receive MTX 3 g/m2 or (Cohort B) will receive MTX 6 g/m^2

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

Drug: leucovorin
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.

Experimental: MTX 6 g/m^2
Patients 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 6 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.
Drug: Voraxaze
Dose of Voraxaze will be 2000 units during cycles 1-4, and 1000 units during cycles 5-8.

Drug: Methotrexate
(Cohort A) will receive MTX 3 g/m2 or (Cohort B) will receive MTX 6 g/m^2

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

Drug: leucovorin
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.




Primary Outcome Measures :
  1. number of patients that have significant reduction of serum methotrexate levels [ Time Frame: 1 year ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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 one or two doses of methotrexate for treatment of primary CNS lymphoma are eligible for enrollment.
  • 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: Prior autologous stem cell transplant as well as prior radiation to the CNS does NOT prevent patients from enrollment into the trial.

NOTE: Patients who have initiated and received up to two doses of MTX treatment will not be excluded from study as long as all pretreatment assessments have been completed within 28 days of trial initiation.

Exclusion Criteria:

  • Patient with SCNSL requiring treatment for extra-CNS disease are excluded.
  • Patient with ocular manifestation of systemic lymphoma 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.
  • 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 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 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 allergic reaction to any of the study drugs involved in this protocol.
  • Patient has undergone prior allogenic stem cell transplant (autologous stem cell transplant is NOT an exclusion).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03684980


Contacts
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Contact: Lauren Schaff, MD 212-610-0485 schaffl@mskcc.org
Contact: Christian Grommes, MD 212-639-4058

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Lauren Schaff, MD    212-610-0485      
Contact: Christian Grommes    212-639-4058      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Lauren Schaff, MD    212-610-0485      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Lauren Schaff, MD    212-610-0485      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Lauren Schaff, MD    212-610-0485      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Lauren Schaff, MD    212-610-0485      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Lauren Schaff, MD         
Contact: Christian Grommes, MD    212-639-4058      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Lauren Schaff, MD    212-610-0485      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
University of Alabama at Birmingham
Investigators
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Principal Investigator: Lauren Schaff, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03684980     History of Changes
Other Study ID Numbers: 18-410
First Posted: September 26, 2018    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Voraxaze (glucarpidase)
B-cell non-Hodgkin‟s lymphoma involving the brain
B-cell non-Hodgkin‟s lymphoma involving spinal cord, and/or leptomeningeal space

Additional relevant MeSH terms:
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Folic Acid Antagonists
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Methotrexate
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors