Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma

A Phase II Trial of Vaccination With Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma

This research study is studying a cancer vaccine called Dendritic Cell/MM Fusion vaccine (DC/MM vaccine) in combination with nivolumab, as a possible treatment for multiple myeloma (MM).

The drugs involved in this study are:

• Dendritic Cell/MM Fusion vaccine (DC/MM vaccine)
• Nivolumab, an immunotherapy drug

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Nivolumab; Biological: DC/myeloma fusions/GM-CSF

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved the DC/MM vaccine as a treatment for any disease.

The FDA has not approved nivolumab for multiple myeloma. A similar immunotherapy drug used in combination with IMiDs (drugs that regulate or modify the immune system) was associated with higher risk of death in another research trial in patients with multiple myeloma; however, nivolumab has been approved for use in several other types of cancers.

The FDA has not approved the combination of nivolumab with the DC/MM vaccine as a treatment for any disease.

In this research study, the investigators wish to determine whether nivolumab administered in combination with the DC/MM vaccine will help promote an immune response against multiple myeloma cells.

An immune response is any reaction by the immune system. It helps the body distinguish itself from substances foreign to it, such as infections and dangerous substances. Cancer cells have unique markers that distinguish them from normal cells, which can potentially serve as targets for the immune system.

The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing those unique markers. Unlike a standard vaccine that is used to prevent infections, cancer vaccines are being studied to see if they can fight cancers that are already in the body. Laboratory studies suggest that when dendritic cells (a type of immune cell that helps to tell your immune system what is good and what is bad) and tumor cells are brought together, the dendritic cells can stimulate immune responses against the tumor.

Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects the body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Monoclonal indicated that this antibody was made in a lab. Nivolumab has been shown to react against cancer cells, including MM cells. The investigators hope that the addition of nivolumab with the DC/MM vaccine will help the body fight MM

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have Patients with relapsed multiple myeloma with prior treatment of an IMID and proteasome inhibitor.
• Age ≥18 years.
• ECOG performance status ≤2
• Patients must have > 20% plasma cells in the bone marrow aspirate differential <30 days prior to enrollment.
• ANC > 1000; Platelets > 75K without transfusional support

• Participants must have normal organ function as defined below:

  • total bilirubin ≤1.5 × institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
  • creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
• The effects of DC/MM fusion and nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is 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 5 months after completion of treatment.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

-Participants who are receiving any other investigational agents.

3.2.2 Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence-Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain >100 mg/L]. Patients with light chain MM detected in the serum by free light chain assay are eligible.

• Patients with Plasma Cell Leukemia
• Because of compromised cellular immunity, patients who have a known human immunodeficiency virus (HIV), active hepatitis C virus (HCV) or active hepatitis B virus (HBV).
• Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix H), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening will be documented by the investigator as not medically relevant.

• Active or prior documented autoimmune or inflammatory disorders including but not limited to the following:

  • GI Disorders: (including inflammatory bowel disease [e.g. ulcerative colitis, Crohn's disease], diverticulitis (with the exception of a prior episode that has resolved), celiac disease, or other serious gastrointestinal chronic conditions associated with diarrhea.
  • Systemic lupus erythematosus

• Wegener's syndrome [granulomatosis with polyangiitis]

  • Myasthenia gravis
  • Graves' disease
  • Rheumatoid arthritis
  • Hypophysitis
  • Uveitis
• The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement; or subjects with psoriasis not requiring systemic treatment.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Note: Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: non-invasive cancer (such as, any in situ cancers) and basal cell or squamous cell carcinoma of the skin.
• Female patients who are pregnant (positive β-HCG) or breastfeeding
• Prior organ transplant requiring immunosuppressive therapy.
• Patients who previously received PD-1 antibody and have experienced toxicities resulting in treatment discontinuation.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nivolumab+DC/myeloma fusions/GM-CSF; Nivolumab will be given every two weeks; The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle

Drug: Nivolumab; Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a type of protein that protects your body against foreign invaders, called antigens, by grabbing hold of antigens to stop them from invading your system. Nivolumab has been shown to react against cancer cells, including MM cells.; Biological: DC/myeloma fusions/GM-CSF; The DC/MM vaccine is an investigational agent that tries to help the immune system recognize and fight against cancer cells, utilizing unique markers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine	We planned to evaluate the immunologic response to treatment in blood and bone marrow. Two patients were treated on protocol and both came off due to disease progression early in the course of therapy (one patient during cycle 1 and one patient during cycle 3.) As such, there is insufficient data to perform what had been planned in correlative science studies so no samples were analyzed. This study has been stopped and no further patients are being enrolled and no further samples are being collected. No data has been obtained for any immune analysis; therefore no immune or clinical data will be reported on this trial.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)	We looked at the two patients who were treated and evaluated their response to treatment.	2 years
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	We evaluated the number of patients who developed a related adverse event as assessed by the CTCAE version 4.0.	2 years
Number of Patients Who Are Alive Without Progression at 2 Years	We calculated the number of patients who were alive without progression at 2 years	2 years

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Bristol-Myers Squibb; Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Jacalyn Rosenblatt, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2019
• Primary Completion (Actual): January 31, 2021
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: December 13, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 18-280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor-Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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