Feasibility of Acquiring Hyperpolarized Imaging in Patients With Primary CNS Lymphoma

NCT04656431 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 20924NCI-2020-085315R01CA239462-02
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary CNS Lymphoma

Keywords

CNS Lymphoma; Hyperpolarized pyruvate (13C)

Outcome Measures

Primary Outcomes (8)

• 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.

  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).

  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.

  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%

  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

  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

  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.

  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.

  1 day

Study Arms (2)

Cohort 1: Hyperpolarized pyruvate (13C)

EXPERIMENTAL

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.

Drug: Hyperpolarized pyruvate (13C); Procedure: Magnetic resonance imaging (MRI)

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.

Drug: Hyperpolarized pyruvate (13C); Procedure: Magnetic resonance imaging (MRI)

Interventions

Hyperpolarized pyruvate (13C) DRUG

Given intravenously (IV) injection prior to imaging

Also known as: 13C

Cohort 1: Hyperpolarized pyruvate (13C); Cohort 2: Hyperpolarized pyruvate (13C)

Magnetic resonance imaging (MRI) PROCEDURE

MRI scan takes an image of brain and/or spinal cord and will take up to 45 minutes to complete

Also known as: MRI

Cohort 1: Hyperpolarized pyruvate (13C); Cohort 2: Hyperpolarized pyruvate (13C)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• James Rubenstein: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Interventions

Magnetic Resonance Spectroscopy

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• James Rubenstein, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wendy Ma

CONTACT

(415) 514-4418; Wendy.Ma@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 7, 2020
• Study Start: June 29, 2021
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2025
• Last Updated: February 9, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)