DARA RVD For High Risk SMM

NCT04775550 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-007
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this research study is to learn whether the combination of daratumumab SC ( Darzalex Faspro), lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone works in treating smoldering multiple myeloma and preventing progression to active or symptomatic multiple myeloma. The names of the study drugs involved in this study are:

• Daratumumab (also called Darzalex Faspro)
• Bortezomib (also called Velcade)
• Lenalidomide (also called Revlimid)
• Dexamethasone

Conditions

High-risk Smoldering Multiple Myeloma; Multiple Myeloma

Keywords

High-risk smoldering Multiple Myeloma; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Proportion of high risk smoldering multiple myeloma (SMM) patients who are MRD negative (MRD-)

  MRD negative disease (MRD-) is defined as zero residual sequence cells detected at a level of one million cells. At time of final analysis, the 2-year MRD- rate will be summarized as a proportion with a 90% exact binomial confidence interval

  2 years

Secondary Outcomes (4)

• Objective Response Rate

  2 Years

• Duration of Response

  2 Years

• Progression-free survival

  2 Years

• Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v4.0

  2 Years

Study Arms (1)

Daratumumab, Bortezomib,Lenalidomide,Dexamethasone

EXPERIMENTAL

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Cycle Length is 28 days. The names of the study drugs involved in this study are: * Daratumumab * Bortezomib * Lenalidomide * Dexamethasone

Drug: Daratumumab; Drug: Bortezomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Subcutaneous, dosage per protocol, dose days vary per cycle. Cycle =28 days

Also known as: Darzalex Faspro

Daratumumab, Bortezomib,Lenalidomide,Dexamethasone

Bortezomib DRUG

Subcutaneous, dosage per protocol, dose days vary per cycle. Cycle =28 days

Also known as: Velcade

Daratumumab, Bortezomib,Lenalidomide,Dexamethasone

Lenalidomide DRUG

Oral, dosage per protocol, days 1-21 per cycle

Also known as: Revlimid

Daratumumab, Bortezomib,Lenalidomide,Dexamethasone

Dexamethasone DRUG

Oral, dosage per protocol, dose days vary per cycle. Cycle =28 days

Also known as: Decadron

Daratumumab, Bortezomib,Lenalidomide,Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Must meet criteria of high-risk smoldering MM as described with one of the below criteria:
• Bone marrow clonal plasma cells ≥10% and any one or more of the following:
• Serum M protein ≥3.0 gm/dL
• Immunoparesis with reduction of two uninvolved immunoglobulin isotypes
• Serum involved/uninvolved free light chain ratio ≥8 (but less than 100)
• Free Light Chain Smoldering Myeloma patients are not excluded
• Progressive increase in M protein level (Evolving type of SMM)\*\*\* Increase in serum monoclonal protein by ≥10% on two successive evaluations within a 6-month period
• Bone marrow clonal plasma cells 50-60%
• Abnormal plasma cell immunophenotype (≥95% of bone marrow plasma cells are clonal) and reduction of one or more uninvolved immunoglobulin isotypes
• High Risk FISH defined as any one or several of the following: t(4;14), t(14;16), t(14;20), del 17p or 1q gain
• MRI with diffuse abnormalities or 1 focal lesion (≥5mm)
• PET-CT with one focal lesion (≥5mm) with increased uptake without underlying osteolytic bone destruction
• OR High-risk per IMWG/Mayo 2018 "20-2-20" Criteria (at least 2 of the following)
• Bone marrow plasmacytosis ≥20%

You may not qualify if:

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational. Prior therapy with bisphosphonate is allowed. Prior radiation therapy to a solitary plasmacytoma is allowed. Prior clinical trials or therapy for smoldering MM or MGUS are allowed but should be discussed with the Principal Investigator.
• 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.
• 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.
• Pregnant or nursing women will be excluded from the study because lenalidomide is an agent with the potential for teratogenic or abortifacient effects.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to daratumumab, bortezomib, lenalidomide, or hyaluronidase
• Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or SARS-CoV-2 (COVID-19).
• Patients who are seropositive because of hepatitis B virus vaccine are eligible.
• Patients who are positive for SARS-COV-2 antibody, HIV1 and 2 antibody, 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.
• Subject has known chronic obstructive pulmonary disease (COPD) or severe, persistent asthma with a Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal.
• Note that PFT/FEV1 testing is required at screening for patients suspected of having COPD or severe, persistent asthma or are suspected of having those conditions or other respiratory impairment

Sponsors & Collaborators

• Omar Nadeem, MD: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (6)

Stamford Hospital

Stamford, Connecticut, 06902, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Brigham Cancer Center - Foxborough

Foxborough, Massachusetts, 02035, United States

Location

Dana-Farber Cancer Institute - Merrimack Valley

Methuen, Massachusetts, 01844, United States

Location

Dana-Farber Brigham Cancer Center

South Weymouth, Massachusetts, 02190, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Omar Nadeem, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 25, 2021
• First Posted: March 1, 2021
• Study Start: March 8, 2021
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): December 8, 2030
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (6)