BHB & CAR-T for Lymphomas

Preliminary Investigation of β-hydroxybutyrate Supplementation for Lymphoma Patients Receiving Anti-CD19 CAR T-cells

The aim of this study is to assess the feasibility of β-hydroxybutyrate (BHB) supplementation in individuals who are receiving therapy for lymphoma with standard-of-care anti-CD19 CAR T-cells (CAR-T) to determine whether BHB supplementation is safe and tolerable in this patient population. Additionally, this study will determine whether BHB supplementation leads to changes the gut microbiome and peripheral blood mononuclear cells (PBMCs). BHB supplementation will be performed through oral administration of HVMN Ketone-IQ, a commercially available BHB supplement, with an active ingredient of R- 1,3-Butanediol, which is converted to BHB.

Study Overview

• Status: Recruiting
• Conditions: Large B-cell Lymphoma
• Intervention / Treatment: Dietary supplement: R-1,3-Butanediol

• Study Type: Interventional
• Enrollment (Estimated): 5
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Brittany Koch, MPH; Phone Number: 215-615-4312; Email: Brittany.Koch@pennmedicine.upenn.edu
• Study Contact Backup: Name: Kaitlin Kennard, BSN, RN; Phone Number: 267-804-4080; Email: Kaitlin.Kennard@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center at University of Pennsylvania
      • Contact: Brittany Koch, MPH; Phone Number: 215-615-4312; Email: Brittany.Koch@pennmedicine.upenn.edu
      • Contact: Kaitlin Kennard, BSN, RN; Phone Number: 267-804-4080; Email: Kaitlin.Kennard@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age of 18 years or older
• History of pathologically-confirmed large B-cell lymphoma (LBCL)
• Planned treatment with a commercially available anti-CD19 CAR-T product (Yescarta or Kymriah)
• Eligible for and with adequate organ function (investigator discretion) and performance status (ECOG PS 2 or less) for standard of care, anti-CD19 CAR-T
• Not enrolled on a clinical trial of bridging therapy prior to CAR-T
• Patients must have a PET/CT scan (preferred), diagnostic CT scan, or MRI with at least one bi-dimensionally measurable lesion (≥ 1.5 cm for nodal lesions or ≥ 1cm for extra- nodal lesions in largest dimension by low-dose computerized tomography [CT] scan with FDG-uptake ≥ liver) documented prior to leukapheresis for CAR-T manufacturing
• Resolution of toxicities from prior therapy to a grade that does not contraindicate trial participation in the opinion of the investigator
• Can provide informed consent
• Willing to comply with all study procedures and available for the duration of the study

Exclusion Criteria:

• Subject is pregnant or breast feeding
• History of allergy to energy drinks
• History of inflammatory bowel disease
• History of type 1 diabetes mellitus or requirement for insulin
• History of chronic kidney disease with an eGFR < 30 mL/min/1.73m2
• Additional second primary malignancy for which the subject is receiving active therapy or that will impede the ability of the investigator to assess lymphoma response

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R-1,3-Butanediol; Participants will take 35mL of HVMN Ketone-IQ by mouth three times daily, with each dose containing 10 grams of R-1,3-Butanediol.	Dietary supplement: R-1,3-Butanediol; R-1,3-Butanediol 35 mL; Other Names: Ketone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Assess number and severity of adverse events as well as number of patients who complete treatment	From CART infusion to day 28 visit after CART

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiome	compare changes in stool microbiome diversity assessed by stool 16S rRNA gene sequencing, metabolomics, qPCR	prior to BHB administration to day 28 visit after CART
Changes in peripheral blood mononuclear cells	compare changes in number and phenotype using flow cytometry, single cell RNAseq, qPCR	prior to BHB administration to day 28 visit after CART

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Elise Chong, MD, Abramson Cancer Center at the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2027

Study Registration Dates

• First Submitted: September 20, 2024
• First Submitted That Met QC Criteria: September 20, 2024
• First Posted (Actual): September 24, 2024

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Organic Chemicals; Ketones; beta-hydroxybutyrate-1,3-butanediol monoester
• Other Study ID Numbers: UPCC 41424; IRB#856611 (Other Identifier: University of Pennsylvania IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available. Explanation: currently under discussion regarding logistics of sharing, data to be shared, and how to access. Some IPD, likely CSR, will be shared after publication. We will finalize a plan by 3/2025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No