Phase I Study of Vaccination With DC/MM Fusion Cells in Combination With BCMA Directed CAR-T Cell Therapy in Relapsed/Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- David Avigan
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Treatment Limiting Toxicity (TLT) Rate
Overview
Brief Summary
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)
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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
Arms & Interventions
DC/MM Fusion Vaccine:
25 participants will be enrolled and will complete the following:
- Baseline visit
- Leukapheresis for dendritic and tumor cell collection
- Standard of care BCMA CAR-T cell therapy
- Cycles 1 through 2 (28 day cycle):
--Day 1: predetermined dose of DC/MM Fusion Vaccine 1x daily and predetermined dose of GM-CSF 1x daily
- Follow up every 3 months starting at month 12 to year 5
Intervention: DC/MM Fusion Vaccine (Biological)
DC/MM Fusion Vaccine:
25 participants will be enrolled and will complete the following:
- Baseline visit
- Leukapheresis for dendritic and tumor cell collection
- Standard of care BCMA CAR-T cell therapy
- Cycles 1 through 2 (28 day cycle):
--Day 1: predetermined dose of DC/MM Fusion Vaccine 1x daily and predetermined dose of GM-CSF 1x daily
- Follow up every 3 months starting at month 12 to year 5
Intervention: GM-CSF (Drug)
Outcomes
Primary Outcomes
Treatment Limiting Toxicity (TLT) Rate
Time Frame: Assessed 28 days post-vaccination.
TLT rate, defined as the proportion of participants who experience treatment-limiting toxicity (TLT) as detailed in Protocol Section 6.1.
Vaccine/Granulocyte-Macrophage Colony-Stimulating Factor(GM-CSF)-Related Adverse Event (AE) Rate
Time Frame: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.
Vaccine/GM-CSF-related AE rate is defined as the proportion of participants who experience any grade AE deemed by investigators as possibly, probably, or definitely related to vaccine or GM-CSF based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Grade 3 or 4 Cytokine Release Syndrome (CRS) Rate
Time Frame: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.
Grade 3 or 4 CRS rate is defined as the proportion of participants who experience grade 3 or 4 CRS based on the American Society of Transplantation and Cellular Therapy (ASTCT) consensus guidelines.
Grade 3 or 4 Immune-effector Cell-associated Neurotoxicity (ICANS) Rate
Time Frame: Assessed during the vaccination period of 8 weeks and then up to 1 year post-vaccination.
Grade 3 or 4 ICANS rate is defined as the proportion of participants who experience grade 3 or 4 ICANS based on the American Society of Transplantation and Cellular Therapy (ASTCT) consensus guidelines.
Secondary Outcomes
- Complete Response (CR) Rate(12 months)
- Measurable Residual Disease (MRD) Negative Rate(12 months)
- Progression-Free Survival (PFS) at 12 months(12 months post-CAR-T cell therapy)
Investigators
David Avigan
Sponsor-Investigator
Beth Israel Deaconess Medical Center