Phase II Study of the CD38 Antibody Daratumumab in Patients With High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma

NCT03236428 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-212
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

Brief Summary

This research study is studying a drug as a possible treatment for Monoclonal Gammopathy of Unknown Significance (MGUS) or Smoldering Multiple Myeloma (SMM). The drug involved in this study is:

• Daratumumab

Conditions

Monoclonal Gammopathy; Smoldering Multiple Myeloma

Keywords

Smoldering Multiple Myeloma; Monoclonal Gammopathy

Outcome Measures

Primary Outcomes (1)

• The Proportion Of Patients In Deep Response

  To determine the proportion of patients who are in VGPR or better after twenty cycles of therapy with Daratumumab. This will be determined at the time of best overall response.

  2 years

Secondary Outcomes (6)

• Objective Response Rate

  2 years

• Duration of Response

  2 years

• Complete Response Rate

  2 years

• Overall Response Rate

  2 years

• Progression Free Survival

  2 years

Study Arms (1)

Daratumumab

EXPERIMENTAL

Daratumumab will be administered by IV infusion weekly during cycles 1 and 2 Daratumumab will be administered by IV infusion every other week during cycles 3 through 6 Daratumumab will be administered by IV infusion monthly during cycles 7 through 20

Drug: Daratumumab

Interventions

Daratumumab DRUG

Daratumumab is a drug that may kill or stop cancer cells from growing through a variety of mechanisms by attaching to the CD38 molecule

Also known as: Darzalex

Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Must meet criteria for high-risk MGUS or low-risk smoldering myeloma as described below:
• High-Risk MGUS
• Must have \<10% plasma cells and \<3.0g/dL M-spike and at least 2 of the following 3 criteria:
• Abnormal free light-chain (FLC) ratio (\<0.26 or \>1.65)
• M-protein concentration (≥1.5 g/dL)
• Non-IgG M protein (including IgA)
• Low-Risk Smoldering Multiple Myeloma
• Must only present with 1 of the following criterion:
• Monoclonal Protein ≥ 3 g/dL
• ≥ 10% Bone Marrow Plasma Cells
• FLC ratio \< 0.125 or \> 8
• No evidence of CRAB criteria† or new criteria of active MM which including the following:
• Increased calcium levels (corrected serum calcium \>0.25 mmol/dL above the upper limit of normal or \>0.275 mmol/dL)
• Renal insufficiency (attributable to myeloma)

You may not qualify if:

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonates is allowed. Prior radiation therapy to a solitary plasmacytoma is allowed.
• Concurrent exposure to any commercially available agents known to be active against SMM and MM.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal.
• Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 \<50% of predicted normal.
• Subject has known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification.
• Subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrollable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing women will be excluded from the study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Daratumumab.
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. Patients who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Major surgery within 4 weeks before enrollment.
• Subject is known or suspected of not being able to comply with the study protocol (eg, because of alcoholism, drug dependency, or psychological disorder). Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Vaccination with live attenuated vaccines within 4 weeks of first study agent administration

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Janssen Pharmaceuticals: collaborator
• Multiple Myeloma Research Consortium: collaborator
• Blood Cancer Research Partnership: collaborator
• The Leukemia and Lymphoma Society: collaborator

Study Sites (6)

Pacific Cancer Care

Monterey, California, 93940, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Insitute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Paraproteinemias; Smoldering Multiple Myeloma

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Neoplasms; Hypergammaglobulinemia

Results Point of Contact

• Title: Senior Clinical Research Program Manager
• Organization: Dana-Farber Cancer Institute

Ashlee_Sturtevant@dfci.harvard.edu

(617) 632-4101

Study Officials

• Irene Ghobrial, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: August 1, 2017
• Study Start: November 24, 2017
• Primary Completion: October 4, 2021
• Study Completion (Estimated): October 4, 2026
• Last Updated: March 27, 2026
• Results First Posted: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)