DC/MM fusion vaccine plus BCMA CAR-T for relapsed or refractory multiple myeloma

Phase I Study of Vaccination With DC/MM Fusion Cells in Combination With BCMA Directed CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma

This trial will test whether adding a personalized DC/MM fusion vaccine (with GM‑CSF) to standard BCMA CAR‑T therapy helps people with relapsed or refractory multiple myeloma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beth Israel Deaconess Medical Center (Academic / other)
• Drugs / interventions: CAR T, CAR-T
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT07377435 on ClinicalTrials.gov

What this trial studies

This Phase I study combines a personalized dendritic cell/tumor (DC/MM) fusion vaccine and GM‑CSF with standard-of-care BCMA-directed CAR‑T therapy in adults with relapsed or refractory multiple myeloma. Participants undergo leukapheresis to collect cells for vaccine manufacture, receive CAR‑T infusion per standard practice, and receive vaccine doses with serial blood tests, imaging, and bone marrow biopsies for monitoring. The trial is designed to characterize safety and look for early signs of added effectiveness in about 25 participants. The DC/MM fusion vaccine is investigational and not FDA-approved for this indication.

Who should consider this trial

Good fit: Adults (≥18 years) with relapsed or refractory multiple myeloma who are eligible for standard-of-care BCMA CAR‑T therapy, have ECOG performance status ≤2, adequate organ function, and ≥20% plasma cells in bone marrow are ideal candidates.

Not a fit: Patients who are not eligible for CAR‑T therapy, have ECOG >2, inadequate organ function, cannot undergo leukapheresis, or are pregnant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could deepen and prolong responses to BCMA CAR‑T therapy for patients with relapsed or refractory multiple myeloma.

How similar studies have performed: BCMA-directed CAR‑T therapies have produced high response rates in relapsed/refractory myeloma, but combining them with personalized DC/MM fusion vaccines is an early approach with limited prior human data.

Eligibility criteria

Inclusion Criteria:

* Patients must be eligible to receive standard of care CAR T-cell therapy for relapsed or refractory multiple myeloma
* Patients must be ≥18 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Patients must have 20% or more plasma cells in the bone marrow core or aspirate differential within 30 days prior to enrollment.
* Patients must have adequate organ function as defined below:

  * Total bilirubin ≤ 1.5 x institutional upper limit of normal
  * AST ≤ 3 x institutional upper limit of normal
  * ALT ≤ 3 x institutional upper limit of normal
  * Creatinine clearance ≥ 40 mL/min for participants with creatinine levels above institutional normal
* The effects of DC/MM fusion vaccine on the developing human fetus are unknown. For this reason, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier methods of birth control or abstinence) prior to study enrollment and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of treatment.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Patients receiving other investigational drugs
* Patients with Plasma Cell Leukemia

  * Patients who have known active uncontrolled infections with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV)
  * Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias. Prior to study entry, any ECG abnormality at screening will be documented by the investigator as not medically relevant.
* Female patients who are pregnant (positive β-HCG) or breastfeeding.
* Prior organ transplant requiring immunosuppressive therapy.
* Uncontrolled intercurrent illness including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
* History of intolerance to CAR-T related drugs or GM-CSF.

Inclusion Criteria Prior to Vaccination with DC/MM Fusions:

* Resolution of all CAR T- related grade 3-4 toxicities
* Successful production of at least 2 vaccines with a minimum of 1 x 106 fusion cells
* Absence of disease progression following CAR T-cell therapy
* ECOG performance status ≤ 2
* Patients must have adequate organ function as defined below:

  * Total bilirubin ≤ 1.5 x institutional upper limit of normal
  * AST ≤ 3 x institutional upper limit of normal
  * ALT ≤ 3 x institutional upper limit of normal
  * Creatinine within normal limits or Creatinine clearance ≥ 40 mL/min for participants with creatinine levels above institutional normal
  * ANC \>1000 in the absence of growth factor support in the prior 7 days
  * Platelet count \>50K without the need for transfusion in the prior 7 days
  * No myeloma-directed therapy following administration of CAR T-cells

Where this trial is running

Boston, Massachusetts

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Jacalyn Rosenblatt, MD — Beth Israel Deaconess Medical Center
• Study coordinator: Jacalyn Rosenblatt, MD

Conditions Multiple Myeloma; Refractory Multiple Myeloma; Relapse Multiple Myeloma; Relapsed Multiple Myeloma; MM