DC/MM Fusion Vaccine With BCMA CAR-T in R/R MM

Официальное название

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

Обзор

This study is to evaluate the safety and effectiveness of dendritic cell DC/MM fusion vaccine in combination with standard of care B-cell maturation antigen (BCMA) CAR-T cell therapy in participants with relapsed/refractory multiple myeloma. The names of the study drugs involved in this study are: * DC/MM fusion vaccine (a type of personalized cancer vaccine) * Granulocyte-macrophage colony-stimulating factor (GM-CSF) (a type of growth factor or hormone)

Подробное описание

This Phase I study is to evaluate the safety and effectiveness of dendritic cell DC/MM fusion vaccine in combination with standard of care B-cell maturation antigen (BCMA) CAR-T cell therapy in participants with relapsed/refractory multiple myeloma. The DC/MM fusion vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells.

The U.S. Food and Drug Administration (FDA) has not approved DC/MM fusion vaccine as a treatment for relapsed or refractory multiple myeloma.

The FDA has approved GM-CSF as a treatment for relapsed or refractory multiple myeloma.

The research study procedures include screening for eligibility, in-clinic visits, collection of dendritic and tumor cells in a process called leukapheresis, blood tests, urine tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, or Positron Emission (PET) scans, X-rays, electrocardiograms (ECGs), bone marrow biopsies and aspirations.

It is expected about 25 people will take part in this research study.

The V Foundation for Cancer Research is providing funding for this study.

Вмешательства

• Биопрепарат DC/MM Fusion Vaccine
  Dendritic Cell and tumor fusion vaccine, via subcutaneous injection (under the skin), per protocol.
• Препарат GM-CSF
  Granulocyte-Macrophage Colony-Stimulating Factor, via subcutaneous injection, per standard of care.

Первичные конечные точки

• Treatment Limiting Toxicity (TLT) Rate [Срок оценки: Assessed 28 days post-vaccination.]
• Vaccine/Granulocyte-Macrophage Colony-Stimulating Factor(GM-CSF)-Related Adverse Event (AE) Rate [Срок оценки: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.]
• Grade 3 or 4 Cytokine Release Syndrome (CRS) Rate [Срок оценки: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.]
• Grade 3 or 4 Immune-effector Cell-associated Neurotoxicity (ICANS) Rate [Срок оценки: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.]

Вторичные конечные точки (3)

• Complete Response (CR) Rate [Срок оценки: 12 months]
• Measurable Residual Disease (MRD) Negative Rate [Срок оценки: 12 months]
• Progression-Free Survival (PFS) at 12 months [Срок оценки: 12 months post-CAR-T cell therapy]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Beth Israel Deaconess Medical Center — Boston

Идентификаторы

NCT: NCT07377435 · 25-799

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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