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Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma

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ClinicalTrials.gov Identifier: NCT04656431
Recruitment Status : Recruiting
First Posted : December 7, 2020
Last Update Posted : December 7, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
James Rubenstein, University of California, San Francisco

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Primary CNS Lymphoma Drug: Hyperpolarized pyruvate (13C) Procedure: Magnetic resonance imaging (MRI) Phase 1

Detailed Description:

PRIMARY OBJECTIVES

  1. 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.
  2. 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.
  3. To define the most appropriate imaging parameters for obtaining 13C data from PCNSL participants (Cohort 1, n=5).
  4. 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

  1. 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.
  2. 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: Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline.

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).

Participants are followed for 48 hours after injection for adverse events. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Pilot Study of Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma
Actual Study Start Date : October 30, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Hyperpolarized pyruvate (13C) Single Image (Cohort 1)
Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) and undergo MRI at baseline
Drug: Hyperpolarized pyruvate (13C)
Given intravenously (IV) injection prior to imaging
Other Name: 13C

Procedure: Magnetic resonance imaging (MRI)
MRI scan takes an image of brain and/or spinal cord and will take up to 45 minutes to complete
Other Name: MRI

Experimental: Hyperpolarized pyruvate (13C) Multiple Images (Cohort 2)

Newly diagnosed PCNSL participants with planned treatment of standard high-dose methotrexate,temozolomide plus rituximab (MT-R) regimen

Images using 13C will be performed both at baseline and after three cycles of standard induction chemotherapy. Participants in Cohort 2 will also have option to undergo an additional imaging at a later time if their cancer progresses.

Drug: Hyperpolarized pyruvate (13C)
Given intravenously (IV) injection prior to imaging
Other Name: 13C

Procedure: Magnetic resonance imaging (MRI)
MRI scan takes an image of brain and/or spinal cord and will take up to 45 minutes to complete
Other Name: MRI




Primary Outcome Measures :
  1. Proportion of participants with treatment-emergent Adverse Events [ Time Frame: Up to 48 hours ]
    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.

  2. Number of participants with abnormal changes in vital signs [ Time Frame: Up to 48 hours ]
    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).

  3. Number of participants with abnormal changes in injection site [ Time Frame: Up to 48 hours ]
    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.

  4. 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%

  5. Pyruvate-to lactate conversion (kPL) [ Time Frame: Up to 48 hours ]
    The kinetics of hyperpolarized [1-13C] pyruvate and 13C- in cancer models using a compressed sensing dynamic MRSI method

  6. 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

  7. 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.

  8. 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.



Information from the National Library of Medicine

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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:

  • For Patients in Cohort 1: Histologically proven PCNSL who have evidence of evaluable disease based on a prior MR scan: measurable disease based on MRI is defined as gadolinium enhancement of a central nervous system (CNS) lymphoma lesion (at least one centimetre (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.

    1. Patients must be > 18 years old and with a life expectancy > 12 weeks.
    2. Patients are eligible provided they had histologic confirmation of CNS non-Hodgkin lymphoma (NHL), DLBCL-type.
    3. 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.
    4. If patient requires dexamethasone, dose must be stable for >1 week prior to MR studies.
    5. Patients cannot have contraindication to MRI examinations or to lumbar puncture. Concomitant involvement of cerebrospinal fluid/leptomeninges and intraocular compartments is allowed.
    6. Patients must have adequate bone marrow function (white blood cell count (WBC) > 3,000/µl, Absolute Neutrophil Count (ANC) > 1,500/mm3, platelet count of > 100,000/mm3, and adequate renal function (creatinine >50 millilitre(ml)/minute) before starting therapy. These tests must be performed within 14 days prior to Hyperpolarized Imaging scan.
    7. 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.
    8. Patients must not have New York Heart Association (NYHA) Grade II or greater congestive heart failure
    9. Patients must not have history of myocardial infarction or unstable angina within 12 months prior to study enrollment.
    10. Patients must be eligible for treatment with high-dose methotrexate (dose between 1 gm/m2 - 8 gm/m2).
    11. 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.
    12. 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.
    13. 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.
    14. 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:

  1. Subjects must be excluded from participating in this study if are not able to comply with study and/or follow-up procedures.
  2. Patients with baseline cardiovascular risk defined as the following:

    1. Poorly controlled hypertension, defined as either systolic >170 or diastolic >110.
    2. Congestive Heart Failure >=Class III
    3. Myocardial infarction within the past year
    4. QT prolong

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): NCT04656431


Contacts
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Contact: Priscilla Chan 877-827-3222 Priscilla.Chan2@ucsf.edu

Locations
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United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Priscilla Chan    877-827-3222    Priscilla.Chan2@ucsf.edu   
Contact: cancertrials@ucsf.edu         
Principal Investigator: James Rubenstein, MD, PhD         
Sponsors and Collaborators
James Rubenstein
National Cancer Institute (NCI)
Investigators
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Principal Investigator: James Rubenstein, MD, PhD University of California, San Francisco
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Responsible Party: James Rubenstein, Principal Investigator, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT04656431    
Other Study ID Numbers: 20924
NCI-2020-08531 ( Registry Identifier: NCI Clinical Trials Reporting Program (CTRP) )
5R01CA239462-02 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2020    Key Record Dates
Last Update Posted: December 7, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 James Rubenstein, University of California, San Francisco:
CNS Lymphoma
Hyperpolarized pyruvate (13C)
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases