Daratumumab Combined With Bortezomib, Cyclophosphamide and Dexamethasone for the Treatment of Multiple Myeloma Patients Presenting With Extramedullary Disease

NCT04166565 | Active Not Recruiting Phase 2

• 2 other identifiers: EMN192019-000991-41
• Study Type: interventional
• Target: 41
• Locations: 3 countries
• Sites: 8

Brief Summary

This trial will try to establish the feasibility and efficacy of the combination of DaraVCD in Multiple Myeloma (MM) patients presenting with extramedullary disease (EMD). The study will be conducted as a Phase II trial. Forty patients will be included in the study cohort. All patients will be followed closely for toxicities and response assessment. After completion of treatment, patients will be followed every 6 months for survival until 5 years after enrolment

Conditions

Multiple Myeloma; Extramedullary Plasmacytoma

Outcome Measures

Primary Outcomes (1)

• CR or better

  the proportion of patients who achieved CR or better

  5 years

Secondary Outcomes (5)

• Duration of Response

  5 years

• Progression Free Survival

  5 years

• Overall Response Rate

  5 years

• Overall Survival

  5 years

• Safety (Adverse Events)

  5 years

Study Arms (1)

Daratumumab/bortezomib/cyclophospamide/dexamethasone (daraVCD)

EXPERIMENTAL

Daratumumab 16 mg/kg will be administered by i.v. infusion. Daratumumab will be administered weekly in Cycles 1 and 2, then every 2 weeks for Cycles 3-6, and thereafter every month up to 36 months. Bortezomib 1.5 mg/m2 bortezomib will be administered by a subcutaneous injection once weekly (Days 1, 8, 15 and 22) in all cycles. Cyclophosphamide 300 mg/m2 will be administered as a p.o. or i.v. weekly dose (Days 1, 8, 15, and 22) in every 28-day cycle (maximum weekly dose 500 mg). Dexamethasone will be administered on Days 1, 2, 8, 9, 15, 16, 22 and 23 in all cycles. On daratumumab infusion days dexamethasone may be administered i.v. or p.o. approximately 1 hour before the daratumumab infusion. On days when daratumumab is not administered, dexamethasone is to be administered p.o.

Drug: Daratumumab; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab 16 mg/kg will be administered by i.v. infusion. Daratumumab will be administered weekly in Cycles 1 and 2, then every 2 weeks for Cycles 3-6, and thereafter every month up to 36 months.

Daratumumab/bortezomib/cyclophospamide/dexamethasone (daraVCD)

Bortezomib DRUG

Bortezomib 1.5 mg/m2 bortezomib will be administered by a subcutaneous injection once weekly (Days 1, 8, 15 and 22) in all cycles.

Also known as: Velcade

Daratumumab/bortezomib/cyclophospamide/dexamethasone (daraVCD)

Cyclophosphamide DRUG

Cyclophosphamide 300 mg/m2 will be administered as a p.o. or i.v. weekly dose (Days 1, 8, 15, and 22) in every 28-day cycle (maximum weekly dose 500 mg). Dexamethasone will be administered on Days 1, 2, 8, 9, 15, 16, 22 and 23 in all cycles. On daratumumab infusion days dexamethasone may be administered i.v. or p.o. approximately 1 hour before the daratumumab infusion. On days when daratumumab is not administered, dexamethasone is to be administered p.o.

Daratumumab/bortezomib/cyclophospamide/dexamethasone (daraVCD)

Dexamethasone DRUG

Dexamethasone will be administered on Days 1, 2, 8, 9, 15, 16, 22 and 23 in all cycles. On daratumumab infusion days dexamethasone may be administered i.v. or p.o. approximately 1 hour before the daratumumab infusion. On days when daratumumab is not administered, dexamethasone is to be administered p.o.

Daratumumab/bortezomib/cyclophospamide/dexamethasone (daraVCD)

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of Multiple Myeloma(MM) (IMWG consensus guidelines)
• Newly diagnosed or relapsed (patients should have received a maximum of one line of prior therapy) patients presenting with extramedullary disease (EMD) of the skin, liver, lungs, central nervous system, lymph nodes or other tissues, but not solely paraskeletal plasmacytoma (expanding soft tissue masses)\* detected by physical exam and confirmed (when required) by Weight Bearing CT/MRI/PET-CT and/or biopsy\*\*. Documentation of plasma cell infiltration is highly recommended unless it requires invasive surgical intervention such as intracerebral infiltration of plasmacytomas.
• \*Note: patients with only paraosseous extension of MM forming soft tissue plasmacytomas are not eligible
• \*\*Note: An additional radiologic assessment at screening is not required to confirm EMD. Documentation in terms of physician's/pathologist's report and/or radiologic assessments performed within 42 days of C1D1 will suffice for the purposes of eligibility. All patients however will undergo a baseline radiologic assessment at C1D1 for response purposes.
• Patients with one prior line of therapy must have:
• achieved a response (PR or better based on investigator's determination of response by the IMWG criteria) to at least one prior regimen.
• documented evidence of PD based on Investigator's determination of response as defined by the IMWG criteria on or after the last line of treatment.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. Note: for patients with central nervous system (CNS) involvement, an ECOG performance status \>2 is also acceptable
• Each patient must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Patients must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
• Patient must have measurable disease of MM as defined by the below criteria:
• IgG MM: Serum M protein level ≥1.0 g/dL or urine M protein level ≥200 mg/24 hours, or
• IgA, IgD, IgE, IgM MM: Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
• Light chain MM, for patients without measurable disease in the serum or urine: Serum immunoglobulin free light chain (FLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
• Reproductive Status

You may not qualify if:

• Solitary plasmacytoma
• Paraosseous extension of MM forming soft tissue plasmacytomas only (without EMD).
• Previous therapy with any anti-CD38 or anti-CS1 monoclonal antibody
• Patients refractory to bortezomib based regimens (PD on or within 60 days of completion of bortezomib OR failure to achieve at least a minimal response \[MR\]) as the prior line of therapy
• Patients who have Bortezomib or Daratumumab hypersensitivity
• Patients who have active or chronic infections
• Patients who have received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before Cycle 1 Day 1 (C1D1). The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before C1D1.
• Previous autologous stem cell transplant (ASCT) within 12 weeks before C1D1.
• Previous allogenic stem cell transplant (alloSCT) regardless of timing.
• Patient has received radiotherapy within 14 days from C1D1. NOTE: Urgent localized radiotherapy for Spinal Cord Compression or Central Nervous System Involvement is allowed.
• Patient 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 patients must be excluded if FEV1 \<50% of predicted normal
• Patient has known moderate or severe persistent asthma within the past 2 years (see) or currently has uncontrolled asthma of any classification. Note: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).
• Severe cardiovascular disease (arrhythmias \[CTCAE Grade 3 or higher\] requiring chronic treatment, congestive heart failure \[New York Heart Association (NYHA) Class III - IV\] or symptomatic ischemic heart disease);
• Severe pulmonary dysfunction (CTCAE grade 3-4, see appendix D);
• Severe neurological or psychiatric disease;

Sponsors & Collaborators

• Stichting European Myeloma Network: lead
• Janssen, LP: collaborator

Study Sites (8)

University of Athens

Athens, Greece

Location

Anticancer Hospital of Thessaloniki

Thessaloniki, Greece

Location

University of Bologna

Bologna, Italy

Location

Univerity of Turin

Torino, Italy

Location

Ankara University

Ankara, Turkey (Türkiye)

Location

Dokuz Eylul University

Balçova, Turkey (Türkiye)

Location

Erciyes University

Kayseri, Turkey (Türkiye)

Location

Marmara University

Pendik, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Cyclophosphamide; Dexamethasone

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 18, 2019
• Study Start: October 31, 2019
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

TU (4); GR (2); IT (2)