Clinical trial NCT03782064: Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma
Official title: A Phase II Trial of Vaccination With Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Dana-Farber Cancer Institute
First posted: 2018-12-20
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Who Develop Immunologic Response to Nivolumab and the DC/MM Fusion Vaccine
timeFrame: 2 years
Secondary outcomes:
measure: Number of Patients Who Achieve a Clinical Response (SD, PR, VGPR, CR)
timeFrame: 2 years
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: 2 years
measure: Number of Patients Who Are Alive Without Progression at 2 Years
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Jacalyn Rosenblatt, MD
role: PRINCIPAL_INVESTIGATOR
References: