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

NCT07564219 | Recruiting

• 1 other identifier: 2025-101551-BO
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma (MM); CAR T Cells; Bispecific Antibodies

Keywords

Ketogenic Diet; beta-hydroxybutyrate (BHB)

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (9)

Arm A 1

EXPERIMENTAL

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

Arm A2

EXPERIMENTAL

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

A3

EXPERIMENTAL

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

A4

NO INTERVENTION

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.

B1

EXPERIMENTAL

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

B2

EXPERIMENTAL

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

B3

EXPERIMENTAL

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

B4

EXPERIMENTAL

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

B 5

NO INTERVENTION

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.

Interventions

Ketogenic diet BEHAVIORAL

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

A3; B4

Ketogenic Drinks BEHAVIORAL

Ketone Performance, DeltaG

Arm A 1; Arm A2; B1; B2; B3

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Medical Center Hamburg-Eppendorf

Hamburg, Free and Hanseatic City of Hamburg, 20251, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Joseph Tintelnot, MD

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Weller, MD

CONTACT

0049 40 7410 0; j.weller@uke.de

Lisa Leypoldt, MD

CONTACT

l.leypoldt@uke.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2026
• First Posted: May 4, 2026
• Study Start: January 30, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Locations

DE (1)