Hyperpolarized Carbon C 13 Pyruvate MRI for the Diagnosis of Patients with Primary Central Nervous System Lymphoma
This phase I trial evaluates the feasibility of using hyperpolarized carbon C 13 pyruvate magnetic resonance imaging (MRI) in diagnosing patients with primary central nervous system lymphoma. This trial aims to see whether MRI using hyperpolarized carbon-13 pyruvate is safe and useful for detecting central nervous system lymphoma and evaluating response to treatment.
Inclusion Criteria
- For Patients in Cohort 1: Histologically proven newly diagnosed or relapsed PCNSL who have evidence of evaluable disease based on a prior MR scan or relapsed central nervous system (CNS) lymphoma: measurable disease based on MRI is defined as gadolinium enhancement of a CNS lymphoma lesion (at least one cm diameter)
- For Patients in Cohort 2: Histologically proven newly diagnosed PCNSL who will receive standard treatment with high-dose methotrexate, temozolomide plus rituximab (MT-R). These criteria will ensure validity of this study in terms of safety, evaluation of clinically and radiographically relevant disease
- Patients must be > 18 years old and with a life expectancy > 12 weeks
- Patients are eligible provided they had histologic confirmation of central nervous system (CNS) non-Hodgkin lymphoma (NHL), diffuse large B-cell lymphoma (DLBCL)-type
- Measurable disease based on MRI that shows gadolinium enhancement of CNS lymphoma lesion, (at least one cm diameter) within two weeks of enrollment, is mandatory. Recent MRI must be eligible for review
- Concomitant involvement of cerebrospinal fluid/leptomeninges and intraocular compartments is allowed
- Creatinine > 50 ml/min (performed within 21 days prior to hyperpolarized imaging scan)
- Patients must not have any significant medical illnesses that in the investigator’s opinion cannot be adequately controlled with appropriate therapy, would compromise the patient’s ability to participate in this study or any disease that will obscure toxicity or dangerously impact response to the imaging agent
- Patients must not have New York Heart Association (NYHA) grade II or greater congestive heart failure
- Patients must be eligible for treatment with high-dose methotrexate (dose between 1 gm/m^2 - 8 gm/m^2)
- Each participant must sign an institutional review board–approved informed consent document in accordance with federal and institutional guidelines. Patients must sign an authorization for release of their protected health information
- This study was designed to include women and minorities but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender. Minorities will actively be recruited to participate. No exclusion to this study will be based on race
- Patients must not have a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for >= 3 years (yrs)
- Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of hyperpolarized imaging scan. Effective contraception (men and women) must be used in subjects of childbearing potential
Exclusion Criteria
- Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04656431.
Locations matching your search criteria
United States
California
San Francisco
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of hyperpolarized 13C magnetic resonance (MR) metabolic imaging as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in primary central nervous system lymphoma (PCNSL) patients.
II. To assess the feasibility of hyperpolarized 13C MR metabolic imaging as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in PCNSL patients.
III. To define the most appropriate imaging parameters for obtaining hyperpolarized 13C data from PCNSL patients.
IV. Evaluate changes in Cohort 2 in imaging pre- and post- high- dose methotrexate (MTX)-based therapy using the parameters found in Cohort 1.
EXPLORATORY OBJECTIVES:
I. To test the hypothesis that genetic markers of NF-kB activation in PCNSL diagnostic specimens correlate with high lactate signal on MR metabolic imaging and with high cerebrospinal fluid (CSF) lactate concentration on baseline pretreatment CSF evaluation.
II. Test the hypothesis that genetic markers of NF-kB activation correlate with a smaller decrease in lactate on repeat metabolomic imaging and in repeat CSF evaluation after standard induction methotrexate-based therapy.
III. Test the hypothesis that genetic markers of NF-kB activation and high lactate signals correlate with lower rate of complete radiographic response on conventional MRI and shorter progression-free survival (PFS).
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI on study.
COHORT II: Patients receive hyperpolarized carbon C 13 pyruvate IV and undergo MRI at baseline, up to 2 weeks after finishing 3 cycles of standard high-dose methotrexate, temozolomide plus rituximab therapy, and at disease progression (if applicable).
After completion of study, patients in Cohort 2 are followed up every 3 months for 2 years after completion of therapy, every 6 months for the next 3 years, and then annually for the next 5 years.
Trial PhasePhase I
Trial Typediagnostic
Lead OrganizationUniversity of California San Francisco
Principal InvestigatorJames Louis Rubenstein
- Primary ID20924
- Secondary IDsNCI-2020-08531, 20-29940
- ClinicalTrials.gov IDNCT04656431