Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03782064
Recruitment Status : Recruiting
First Posted : December 20, 2018
Last Update Posted : June 3, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Myrna Nahas, Dana-Farber Cancer Institute

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

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Nivolumab Biological: DC/myeloma fusions/GM-CSF Phase 2

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


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Vaccination With Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma
Actual Study Start Date : February 22, 2019
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Nivolumab

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.




Primary Outcome Measures :
  1. Number of patients who develop immunologic response to nivolumab and the DC/MM fusion vaccine [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Number of patients who achieve a clinical response (SD, PR, VGPR, CR) [ Time Frame: 2 years ]
  2. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 years ]
  3. Number of patients who are alive without progression at 2 years [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03782064


Contacts
Layout table for location contacts
Contact: Myrna Nahas, MD 617-667-1669 mnahas1@bidmc.harvard.edu
Contact: Elisabeth Dwyer, RN 617-667-1957 edwyer3@bidmc.harvard.edu

Locations
Layout table for location information
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Myrna Nahas, MD    617-667-1669    mnahas1@bidmc.harvard.edu   
Principal Investigator: Myrna Nahas, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Principal Investigator: Myrna Nahas, MD Beth Israel Deaconess Medical Center

Layout table for additonal information
Responsible Party: Myrna Nahas, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03782064     History of Changes
Other Study ID Numbers: 18-280
First Posted: December 20, 2018    Key Record Dates
Last Update Posted: June 3, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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: [contact information for 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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: Requests may be directed to: [contact information for Sponsor-Investigator or designee].

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Myrna Nahas, Dana-Farber Cancer Institute:
Multiple Myeloma

Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Nivolumab
Sargramostim
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs