BEAM-MM - β-Hydroxybutyrate-Enhanced Adaptive Immunity in Multiple Myeloma (BEAM-MM)

This study investigates whether raising blood levels of beta-hydroxybutyrate (BHB) - a natural molecule produced by the body during fasting or a low-carbohydrate diet - is safe and feasible and can improve the effectiveness of immunotherapy in patients with multiple myeloma, while remaining safe and well-tolerated. Patients will be randomly assigned to one of four intervention groups or a control group. The intervention groups will either follow a ketogenic diet (less than 10% of calories from carbohydrates) or receive oral supplementation with deltaG® Ketone Monoester Performance [(R)-3-hydroxybutyl (R)-3-hydroxybutyrate; CAS 1208313-97-6; TdeltaS Global, Inc., Oxford, UK], administered orally three times daily at either a low dose (13.5 g per serving, 40.5 g/day) or a high dose (25 g per serving, 75 g/day), in accordance with the FDA GRAS-approved dosing range. The control group will receive standard nutritional care. The study includes two parts: Part A enrolls patients receiving bispecific antibody treatment, and Part B enrolls patients receiving CAR-T cell therapy. Both dosing levels are applied in each part.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma (MM); CAR T Cells; Bispecific Antibodies
• Intervention / Treatment: Behavioral: Ketogenic Drinks; Behavioral: Ketogenic diet

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jan Weller, MD; Phone Number: 0049 40 7410 0; Email: j.weller@uke.de
• Study Contact Backup: Name: Lisa Leypoldt, MD; Email: l.leypoldt@uke.de

Study Locations

• Germany
  • Free and Hanseatic City of Hamburg
    • Hamburg, Free and Hanseatic City of Hamburg, Germany, 20251
      • Recruiting
      • University Medical Center Hamburg-Eppendorf
      • Contact: Jan Weller, MD; Email: j.weller@uke.de

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Multiple Myeloma with indication for CAR-T cell therapy with Ciltacabtagene autoleucel (target antigen: BCMA) or a BCMA-directed bispecific antibody (e.g., Teclistamab, Elranatamab, Linvoseltamab).
• Age ≥18 years on the day the informed consent is signed.

Exclusion Criteria:

• Active infection requiring systemic therapy.
• Known history of infection with Human Immunodeficiency Virus (HIV) or Hepatitis.
• Significant short-term weight loss (>10% within the last 6 weeks).
• ECOG Performance Status ≥2.
• Prior immunoeffector cell therapy (CAR-T cell therapy or bispecific antibodies).
• Active immunosuppression due to another condition (e.g., autoimmune disease, second malignancy).
• Very high tumor burden with high risk for tumor lysis syndrome, as determined by myeloma-specific markers or markedly elevated LDH (per the treating myeloma team).
• Women of childbearing potential in whom pregnancy cannot be reliably excluded prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A 1; Bispecific Antibody - Arm A1 - Ketone Monoester Low Dose Ketone Performance, DeltaG: 3 × 37 ml/day (≈3 × 13.5 g D-BHB; 3 × 39 g DeltaG drink) for 4 weeks, starting Day -1 before bispecific antibody therapy. Drink times: 08:00, 12:00, 16:00.	Behavioral: Ketogenic Drinks; Ketone Performance, DeltaG
Experimental: Arm A2; Bispecific Antibody - Arm A2 - Ketone Monoester High Dose Ketone Performance, DeltaG: ≈3 × 68.5 ml/day (≈3 × 25 g D-BHB; 3 × 72 g DeltaG drink) for 4 weeks, starting Day -1 before bispecific antibody therapy. Maximum dose per GRAS designation. Drink times: 08:00, 12:00, 16:00.	Behavioral: Ketogenic Drinks; Ketone Performance, DeltaG
Experimental: A3; Bispecific Antibody - Arm A3 - Ketogenic Diet Ketogenic diet per protocol of Hirschberger et al. EMBO Molecular Medicine 2021 for 4 weeks, starting Day -1 before bispecific antibody therapy.	Behavioral: Ketogenic diet; Induction of a stable ketogenic metabolic state to increase blood BHB levels in order to improve T-cell function through immunometabolic reprogramming. Duration: 4 weeks (28 days) Macronutrient distribution: Carbohydrates: <10% of daily caloric intake (approx. 20-30 g/day); Fats: 70-75% of daily caloric intake; Proteins: 15-20% of daily caloric intake
No Intervention: A4; Bispecific Antibody - Arm A4 - Control Group No dietary intervention. Standard-of-care bispecific antibody therapy. Translational control samples and clinical control data collected per follow-up schedule.
Experimental: B1; CAR-T - Arm B1 - Ketone Monoester Low Dose Ketone Performance, DeltaG: 3 × 37 ml/day (≈3 × 13.5 g D-BHB; 3 × 39 g DeltaG drink) for 4 weeks, starting Day -1 before CAR-T reinfusion. Drink times: 08:00, 12:00, 16:00.	Behavioral: Ketogenic Drinks; Ketone Performance, DeltaG
Experimental: B2; CAR-T - Arm B2 - Ketone Monoester Low Dose (Apheresis + Reinfusion) Ketone Performance, DeltaG: 3 × 37 ml/day (≈3 × 13.5 g D-BHB; 3 × 39 g DeltaG drink). Phase 1: 1 week around apheresis (Day -6 to Day +1 of apheresis). Phase 2: 4 weeks starting Day -1 before CAR-T reinfusion. Drink times: 08:00, 12:00, 16:00.	Behavioral: Ketogenic Drinks; Ketone Performance, DeltaG
Experimental: B3; CAR-T - Arm B3 - Ketone Monoester High Dose (Reinfusion only) Ketone Performance, DeltaG: ≈3 × 68.5 ml/day (≈3 × 25 g D-BHB; 3 × 72 g DeltaG drink) for 4 weeks, starting Day -1 before CAR-T reinfusion (no apheresis phase). Maximum dose per GRAS. Drink times: 08:00, 12:00, 16:00.	Behavioral: Ketogenic Drinks; Ketone Performance, DeltaG
Experimental: B4; CAR-T - Arm B4 - Ketogenic Diet Ketogenic diet per protocol of et al. EMBO Molecular Medicine 2021 for 4 weeks, starting Day -1 before CAR-T reinfusion.	Behavioral: Ketogenic diet; Induction of a stable ketogenic metabolic state to increase blood BHB levels in order to improve T-cell function through immunometabolic reprogramming. Duration: 4 weeks (28 days) Macronutrient distribution: Carbohydrates: <10% of daily caloric intake (approx. 20-30 g/day); Fats: 70-75% of daily caloric intake; Proteins: 15-20% of daily caloric intake
No Intervention: B 5; Arm B5 - Control Group No dietary intervention. Standard-of-care CAR-T cell therapy (Ciltacabtagene autoleucel). Translational control samples and clinical control data collected per follow-up schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	No occurrence of Cytokine Release Syndrome (CRS) Grade ≥3 or neurotoxicity (ICANS) Grade ≥3, AND completion of the full 28-day intervention in ≥80% of participants per arm (≥4/5 per arm).	Day 0 to 28 of the intervention
CAR-T-Cell Expansion	Number of CAR-T-Cells per ml of blood	Day 7 after infusion
Effector Cytokines	Protein abundance per ml of blood or cytokines signature of effector cells	Day 1 or 3 after bispecfiic antibody treatment

Collaborators and Investigators

• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Joseph Tintelnot, MD, Universitatsklinikum Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Ketogenic Diet; beta-hydroxybutyrate (BHB)
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Carbohydrate-Restricted; Diet, Ketogenic
• Other Study ID Numbers: 2025-101551-BO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No