Hyperpolarized MRI for CNS Lymphoma

Overseen By Wendy Ma

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: James Rubenstein

Must be taking: Methotrexate, Temozolomide, Rituximab

Disqualifiers: Congestive heart failure, Other cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: Up to 4 months

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of using MRI scans to diagnose and monitor primary central nervous system lymphoma (PCNSL), a type of brain cancer. The researchers aim to determine if a special carbon compound, Hyperpolarized pyruvate (13C), can enhance MRI effectiveness in detecting this cancer and tracking treatment progress. The trial includes two groups: one with newly diagnosed patients and another with those whose cancer has returned. Individuals diagnosed with PCNSL who are receiving or planning to receive standard treatments might be eligible to join. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are in Cohort 2, you will receive specific treatments like high-dose methotrexate, temozolomide, and rituximab.

What prior data suggests that hyperpolarized carbon C 13 pyruvate MRI is safe for diagnosing CNS lymphoma?

Research has shown that using a special form of carbon-13 in MRI scans is safe for people. Early studies on humans demonstrated that injecting this substance does not cause major harm or side effects. This method has also been tested in other conditions, such as prostate cancer, with good results. It appears to be well-tolerated, making it a potentially safe choice for patients interested in joining trials for detecting and monitoring central nervous system lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using hyperpolarized pyruvate (13C) in MRI for CNS lymphoma because it offers a new way to visualize cancer metabolism in real-time. This technique enhances MRI images, allowing doctors to see how the tumor is responding to treatment much earlier than traditional methods. Unlike standard imaging, which relies on structural changes, this approach focuses on metabolic activity, potentially leading to more precise and timely adjustments in therapy.

What evidence suggests that hyperpolarized MRI is effective for diagnosing CNS lymphoma?

Research has shown that a special MRI using hyperpolarized carbon-13 pyruvate can detect tumors and assess their severity. This imaging method excels at identifying hidden tumors and evaluating treatment effectiveness early. Some studies suggest it can help determine tumor aggressiveness by identifying different lesion grades. For brain and central nervous system (CNS) conditions, researchers have explored its ability to track changes. Although specific data for CNS lymphoma is limited, this method appears promising based on its success in similar conditions. Participants in this trial will receive hyperpolarized carbon-13 pyruvate and undergo MRI to evaluate its effectiveness in detecting and monitoring CNS lymphoma. ^{1 3 6 7 8}

Who Is on the Research Team?

James Rubenstein, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with primary central nervous system lymphoma, who have a life expectancy of more than 12 weeks. They must have measurable disease on MRI and adequate kidney function. It's not for those with significant medical illnesses, heart failure, other cancers within the last 3 years (except certain skin cancers or cervical carcinoma in-situ), pregnant or breastfeeding women, or anyone unable to follow study procedures.

Inclusion Criteria

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.

I have a confirmed primary CNS lymphoma with a lesion over 1cm visible on MRI.

My cancer is a type of non-Hodgkin lymphoma in the brain.

Exclusion Criteria

Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging

Participants receive hyperpolarized carbon C 13 pyruvate intravenously and undergo MRI at baseline

1 day

1 visit (in-person)

Treatment

Participants in Cohort 2 receive standard high-dose methotrexate, temozolomide plus rituximab therapy, followed by MRI imaging

Up to 4 months

Multiple visits (in-person) for chemotherapy and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 3 months for 2 years, every 6 months for the next 3 years, and then annually for the next 5 years

Up to 10 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Hyperpolarized pyruvate (13C)
• Magnetic resonance imaging (MRI)

Trial Overview The trial is testing the safety and usefulness of a new type of MRI that uses hyperpolarized carbon C 13 pyruvate to diagnose CNS lymphoma and monitor treatment response. Participants will undergo this special imaging to see if it provides clear pictures of their condition.

How Is the Trial Designed?

Group I: Cohort 2: Hyperpolarized pyruvate (13C) Experimental Treatment 2 Interventions

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.

Group II: Cohort 1: Hyperpolarized pyruvate (13C) Experimental Treatment 2 Interventions

Histologically proven relapsed PCNSL patients 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.

Who Is Running the Clinical Trial?

James Rubenstein

Lead Sponsor

Trials

3

Recruited

70+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Hyperpolarized 13C-MRI, which enhances the detection of tumor metabolism by 4-5 orders of magnitude, can track the metabolism of hyperpolarized [1-13C]pyruvate in cancer patients, providing insights into tumor activity and response to treatment.

Combining HP 13C-MRI with traditional 1H-MRI allows for detailed anatomical imaging and functional tumor analysis, potentially enabling early identification of patients who are not responding to therapies, although cost and technical challenges need to be addressed for broader clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized Carbon-13 MRI in Breast Cancer. Woitek, R., Brindle, KM.[2023]

The study demonstrated that hyperpolarized carbon-13 (HP-13C) metabolic imaging is safe and well-tolerated in pediatric patients with brain tumors, with no adverse events reported during the imaging process.

HP-13C imaging successfully showed the brain's metabolism of HP [1-13C]pyruvate, indicating its potential as a useful tool for assessing metabolic changes in pediatric CNS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperpolarized 13C Metabolic Imaging in Pediatric Patients with Diffuse Intrinsic Pontine Glioma and Other CNS Cancers. Autry, AW., Park, I., Kline, C., et al.[2022]

This study successfully used MR spectroscopic imaging of hyperpolarized [2-(13)C]pyruvate to visualize metabolic changes in glioma-bearing rat brains, revealing higher lactate and lower glutamate levels in tumors compared to normal brain tissue.

Administration of dichloroacetate increased glutamate levels in both tumor and normal brain tissue, indicating its potential to modulate mitochondrial metabolism in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model. Park, JM., Josan, S., Jang, T., et al.[2018]

This study is the first to use hyperpolarized 13C MRI to visualize and measure how the human brain processes [2-13C]pyruvate, providing insights into cerebral energy metabolism.

In a trial involving 5 healthy volunteers, the technique allowed for the simultaneous assessment of glycolytic and oxidative metabolism by quantifying the conversion rates of pyruvate to lactate and glutamate, highlighting its potential for advanced metabolic imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized [2-13C]pyruvate MR molecular imaging with whole brain coverage. Chung, BT., Kim, Y., Gordon, JW., et al.[2023]

Hyperpolarized 13C magnetic resonance spectroscopic (MRS) imaging, particularly using [1-13C]pyruvate, allows for non-invasive real-time detection of metabolic processes, such as lactate and bicarbonate production, without ionizing radiation.

This technique has shown potential in clinical studies for assessing metabolic changes in conditions like cancer and heart ischemia, indicating its future role in advanced metabolic imaging despite needing further technical improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized MRI - An Update and Future Perspectives. Jørgensen, SH., Bøgh, N., Hansen, E., et al.[2022]

Hyperpolarized [1-(13)C]pyruvate can effectively detect treatment responses in glioma tumors, which is challenging with traditional imaging methods like PET due to interference from normal brain tissue signals.

In a rat model, significant lactate labeling was observed in glioma tumors after treatment, with a notable decrease in the ratio of tumor lactate to blood pyruvate signal following whole brain irradiation, indicating a potential response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detecting response of rat C6 glioma tumors to radiotherapy using hyperpolarized [1- 13C]pyruvate and 13C magnetic resonance spectroscopic imaging. Day, SE., Kettunen, MI., Cherukuri, MK., et al.[2021]

Hyperpolarized MRI using [1-13C] pyruvate can effectively characterize energy metabolism in the human brain and identify altered cancer metabolism in brain tumors, as evidenced by the production of HP lactate from HP pyruvate.

This method shows promise as a quantitative metabolic biomarker for assessing tumor response, correlating well with standard clinical imaging techniques like MRI and PET/CT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients. Miloushev, VZ., Granlund, KL., Boltyanskiy, R., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04656431

Feasibility of Acquiring Hyperpolarized Imaging in Patients ... This trial aims to see whether MRI using hyperpolarized carbon-13 pyruvate is safe and useful for detecting central nervous system lymphoma and evaluating ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10546364/

Hyperpolarized Carbon 13 MRI: Clinical Applications and ... Clinical hyperpolarized carbon 13 MRI has been shown to identify occult tumors, stratify lesions based on histologic grade, and detect early response to ...

3. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/13c-pyruvate-ib.pdf

Hyperpolarized Pyruvate (13C) Injection Hyperpolarized Carbon C 13 Pyruvate in. Diagnosing Glioma in Patients with ... 5.1.3.4 Effects on the Central Nervous System (CNS) and general physiology.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8067176/

Comprehensive Literature Review of Hyperpolarized ... This review provides a comprehensive assessment of the development of hyperpolarized (HP) carbon-13 metabolic MRI from the early days to the present

5. mdpi.com mdpi.com/2072-6694/16/2/354

Advanced Hyperpolarized 13C Metabolic Imaging Protocol ... This study aimed to implement a multimodal 1 H/HP- 13 C imaging protocol to augment the serial monitoring of patients with glioma.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6260457/

Hyperpolarized 13C MRI: Path to Clinical Translation in ... The first-in-human study convincingly demonstrated that injection of HP [1-13C]pyruvate is safe and that imaging metabolic products of hyperpolarized [1-13C] ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7986146/

Comparison of 13C MRI of hyperpolarized [1‐13C]pyruvate ... Hyperpolarized [1‐13C]pyruvate has been used clinically with promising applications, such as disease staging in prostate cancer, , and for ...

8. withpower.com withpower.com/trial/phase-1-lymphoma-5-2021-116ca

Hyperpolarized MRI for CNS 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 ...