Primary CNS LymphomaPhase 1NCT04656431
Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma
A Phase 1 study testing Hyperpolarized pyruvate (13C) and Magnetic resonance imaging (MRI) in people with Primary CNS Lymphoma, run by James Rubenstein at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary CNS Lymphoma
- What is being tested?
- Hyperpolarized pyruvate (13C) and Magnetic resonance imaging (MRI)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2021to 31 Mar 2027
- Phase
- 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
- For Patients in Cohort 1: Histologically proven relapsed PCNSL who have evidence of evaluable disease based on a prior MR scan, or relapsed CNS lymphoma: measurable disease based on MRI is defined as gadolinium enhancement of a CNS lymphoma lesion (at least one centimeter (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.
- To be included in the study all subjects must also meet the following criteria:
- Patients must be > 18 years old and with a life expectancy > 12 weeks.
- Patients are eligible provided the participant had histologic confirmation of CNS non-Hodgkin lymphoma (NHL), 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.
Show all 15Show fewer
- Concomitant involvement of cerebrospinal fluid/leptomeninges and intraocular compartments is allowed.
- Patients must have adequate renal function (creatinine >50 ml/min) before starting therapy. These tests must be 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 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.
Who cannot join
- 1. Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Wendy Ma, (415) 514-4418, Wendy.Ma@ucsf.edu
877-827-3222, cancertrials@ucsf.edu
About this study
Official title: Pilot Study of Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS 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.
Read the detailed description
PRIMARY OBJECTIVES
- To determine the safety and tolerability 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 participants with PCNSL.
- To assess the feasibility of hyperpolarized 13C as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in PCNSL participants.
- To define the most appropriate imaging parameters for obtaining 13C data from PCNSL participants (Cohort 1, n=5).
- To evaluate changes in Cohort 2 in imaging pre- and post- high-dose methotrexate, temozolomide plus rituximab (MTX-R) based therapy using the parameters found in Cohort 1
EXPLORATORY OBJECTIVES
- To test the hypothesis that genetic markers of nuclear factor kappa light chain enhancer of activated B cells (NF-kB) activation in PCNSL diagnostic specimens correlate with high lactate signal on metabolic imaging and with high cerebrospinal fluid (CSF) lactate concentration on baseline pre-treatment CSF evaluation.
- To test the hypothesis that genetic markers of NF-kB activation correlate with a smaller decrease in lactate on repeat metabolic magnetic resonance (MR) imaging and in repeat CSF evaluation after standard induction methotrexate-based therapy and 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: Participants are assigned to 1 of 2 cohorts.
COHORT I: Participants receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.
COHORT II: Participants 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). An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.
Participants are followed for 1 hours after injection for adverse events. After completion of study, participants 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.
- Conditions
- Primary CNS Lymphoma
- Being tested
- Hyperpolarized pyruvate (13C), Magnetic resonance imaging (MRI)
- Keywords
- CNS Lymphoma, Hyperpolarized pyruvate (13C)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperpolarized pyruvate (13C)Drug
Also called 13C
Given intravenously (IV) injection prior to imaging
Magnetic resonance imaging (MRI)Procedure or surgery
Also called MRI
MRI scan takes an image of brain and/or spinal cord and will take up to 45 minutes to complete
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Hyperpolarized pyruvate (13C) | Experimental | Histologically proven relapsed PCNSL or relapsed CNS lymphoma participants will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan. |
| Cohort 2: Hyperpolarized pyruvate (13C) | Experimental | Newly diagnosed PCNSL participants with planned treatment of standard high-dose methotrexate,temozolomide plus rituximab (MT-R) regimen will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline and again after three cycles of of standard induction chemotherapy. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan. Participants in Cohort 2 will also have option to undergo an additional imaging at a later time if the participant's cancer progresses. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of participants with treatment-emergent Adverse Events
The Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) will be used to classify and graded any adverse events that occur after the participant has received the hyperpolarized 13C injection.
Measured: 1 day
Number of participants with abnormal changes in vital signs
Clinically significant changes in heart rate and blood pressure will be measured pre- and 10 minutes, 1 hour, 24 hours, and 48 hours post- injection as a measure of safety. The occurrence of changes from baseline, at each post-administration time point, greater than a pre-specified magnitude (20 mm Hg for systolic blood pressure, 10 mm Hg for diastolic blood pressure, 10 beats per minute for heart rate).
Measured: 1 day
Number of participants with abnormal changes in injection site
Injection site will be monitored for evidence of inflammation or infection. Abnormal injection site findings include, but are not limited to, extravasation, bleeding, hematoma, redness, and infection as a measure of safety.
Measured: 1 day
Percent of eligible patients that complete the study
The percentage of participants whom complete the study will be used to determine feasibility with a goal of at least 50%
Measured: Up to 4 months
Pyruvate-to lactate conversion (kPL)
The kinetics of hyperpolarized [1-13C] pyruvate and 13C- in cancer models using a compressed sensing dynamic MRSI method
Measured: 1 day
Number of participants with response
Radiographic confirmed response with state-of-the-art MRI exam (including diffusion imaging, contrast-enhanced MRI and hydrogen magnetic resonance spectroscopic imaging (H1-MRSI) Determination of response status (complete response, partial response or stable disease) as standard will be made at 4 months after initiation of therapy
Measured: Up to 4 months
Signal Amplitudes
Hyperpolarization of 13C pyruvate, using dynamic nuclear polarization (DNP), enhances nuclear magnetic resonance (NMR) signals. The greater the amplitude of the signal, the larger the number of protons in the image and the brighter the signal will appear.
Measured: 1 day
Time Dynamics
For the 2D dynamic data, the time resolution will be 3-5s. For the 3D single time point data the start time will be adjusted based upon when it is anticipated that the lactate/pyruvate will be at a maximum.
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2020
- Study start29 Jun 2021
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary CNS LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- James Rubenstein
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, James Rubenstein, University of California, San Francisco
- Investigators
- James Rubenstein, MD, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04656431
- Sponsor's protocol ID
- 20924
- Other IDs
- NCI-2020-08531, 5R01CA239462-02
- Status last verified
- Jan 2026
- First submitted
- 30 Nov 2020
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma
- ClinicalTrials.gov ID
- NCT04656431
- Acronym / sponsor ID
- 20924
- Conditions
- Primary CNS Lymphoma
- Keywords
- CNS Lymphoma, Hyperpolarized pyruvate (13C)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- James RubensteinUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 29 Jun 2021 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 7 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES
- To determine the safety and tolerability 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 participants with PCNSL.
- To assess the feasibility of hyperpolarized 13C as a new and unique tool in the evaluation of tumor burden and detecting early response to standard therapy in PCNSL participants.
- To define the most appropriate imaging parameters for obtaining 13C data from PCNSL participants (Cohort 1, n=5).
- To evaluate changes in Cohort 2 in imaging pre- and post- high-dose methotrexate, temozolomide plus rituximab (MTX-R) based therapy using the parameters found in Cohort 1
EXPLORATORY OBJECTIVES
- To test the hypothesis that genetic markers of nuclear factor kappa light chain enhancer of activated B cells (NF-kB) activation in PCNSL diagnostic specimens correlate with high lactate signal on metabolic imaging and with high cerebrospinal fluid (CSF) lactate concentration on baseline pre-treatment CSF evaluation.
- To test the hypothesis that genetic markers of NF-kB activation correlate with a smaller decrease in lactate on repeat metabolic magnetic resonance (MR) imaging and in repeat CSF evaluation after standard induction methotrexate-based therapy and 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: Participants are assigned to 1 of 2 cohorts.
COHORT I: Participants receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.
COHORT II: Participants 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). An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan.
Participants are followed for 1 hours after injection for adverse events. After completion of study, participants 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Hyperpolarized pyruvate (13C) | Experimental | –Histologically proven relapsed PCNSL or relapsed CNS lymphoma participants will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan. |
| Cohort 2: Hyperpolarized pyruvate (13C) | Experimental | –Newly diagnosed PCNSL participants with planned treatment of standard high-dose methotrexate,temozolomide plus rituximab (MT-R) regimen will receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline and again after three cycles of of standard induction chemotherapy. An optional second HP 13C pyruvate injection and MRI acquisition will be offered on same day following completion of the first scan. Participants in Cohort 2 will also have option to undergo an additional imaging at a later time if the participant's cancer progresses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- For Patients in Cohort 1: Histologically proven relapsed PCNSL who have evidence of evaluable disease based on a prior MR scan, or relapsed CNS lymphoma: measurable disease based on MRI is defined as gadolinium enhancement of a CNS lymphoma lesion (at least one centimeter (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 the participant had histologic confirmation of CNS non-Hodgkin lymphoma (NHL), 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.
Key exclusion criteria (1 listed)
- 1. Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hyperpolarized pyruvate (13C)Also: 13CGiven intravenously (IV) injection prior to imaging | Drug | – |
| Magnetic resonance imaging (MRI)Also: MRIMRI scan takes an image of brain and/or spinal cord and will take up to 45 minutes to complete | Procedure or surgery | – |
Primary outcome
Proportion of participants with treatment-emergent Adverse Events
Time frame: 1 day
The Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) will be used to classify and graded any adverse events that occur after the participant has received the hyperpolarized 13C injection.
Number of participants with abnormal changes in vital signs
Time frame: 1 day
Clinically significant changes in heart rate and blood pressure will be measured pre- and 10 minutes, 1 hour, 24 hours, and 48 hours post- injection as a measure of safety. The occurrence of changes from baseline, at each post-administration time point, greater than a pre-specified magnitude (20 mm Hg for systolic blood pressure, 10 mm Hg for diastolic blood pressure, 10 beats per minute for heart rate).
Number of participants with abnormal changes in injection site
Time frame: 1 day
Injection site will be monitored for evidence of inflammation or infection. Abnormal injection site findings include, but are not limited to, extravasation, bleeding, hematoma, redness, and infection as a measure of safety.
Percent of eligible patients that complete the study
Time frame: Up to 4 months
The percentage of participants whom complete the study will be used to determine feasibility with a goal of at least 50%
Pyruvate-to lactate conversion (kPL)
Time frame: 1 day
The kinetics of hyperpolarized [1-13C] pyruvate and 13C- in cancer models using a compressed sensing dynamic MRSI method
Number of participants with response
Time frame: Up to 4 months
Radiographic confirmed response with state-of-the-art MRI exam (including diffusion imaging, contrast-enhanced MRI and hydrogen magnetic resonance spectroscopic imaging (H1-MRSI) Determination of response status (complete response, partial response or stable disease) as standard will be made at 4 months after initiation of therapy
Signal Amplitudes
Time frame: 1 day
Hyperpolarization of 13C pyruvate, using dynamic nuclear polarization (DNP), enhances nuclear magnetic resonance (NMR) signals. The greater the amplitude of the signal, the larger the number of protons in the image and the brighter the signal will appear.
Time Dynamics
Time frame: 1 day
For the 2D dynamic data, the time resolution will be 3-5s. For the 3D single time point data the start time will be adjusted based upon when it is anticipated that the lactate/pyruvate will be at a maximum.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2026.
- Individual participant dataSharing planned: No
Related trials for Primary CNS Lymphoma
RecruitingPhase 2
Ibrutinib Combination Therapy in Transplant Ineligible Individuals With Newly Diagnosed Primary CNS Lymphoma
Non-hodgkin Lymphoma
RecruitingPhase 1
Glofitamab With Obinutuzumab Pre-treatment for the Treatment of Central Nervous System Lymphoma
Primary Central Nervous System Lymphoma, Secondary Central Nervous System Lymphoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 2
A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma
Lymphoma
Not yet recruitingPhase 1/2
Multi-CAR-T Cells Targeting B Cell Lymphomas
B Cell Lymphoma (BCL)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James Rubenstein, MD, PhD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hyperpolarized pyruvate (13C) and Magnetic resonance imaging (MRI) in people with Primary CNS Lymphoma, run by James Rubenstein at 1 site 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 15 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 14 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Wendy Ma ((415) 514-4418, Wendy.Ma@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with treatment-emergent Adverse Events (time frame: 1 day). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jul 2026.