A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens

NCT03412565 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: CR1084352017-004203-4154767414MMY2040
• Study Type: interventional
• Target: 265
• Locations: 9 countries
• Sites: 64

Brief Summary

The purpose of this study is to evaluate the clinical benefit of subcutaneous (SC) daratumumab administered in combination with standard multiple myeloma (MM) regimens in participants with MM as measured by overall response rate (ORR) or very good partial response (VGPR) or better rate.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)

  ORR was defined as the percentage of participants who achieved partial response (PR) or better according to international myeloma working group (IMWG) criteria. IMWG criteria for PR: greater than or equal to (\>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to less than (\<) 200 milligrams (mg) per 24 hours, If the serum and urine M-protein are not measurable, a decrease of \>=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the M-protein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, \>=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was \>=30%. In addition to the above criteria, if present at baseline, a \>=50% reduction in the size of soft tissue plasmacytomas is also required.

  Up to 2 years 3 months

• D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response

  VGPR or better rate was defined as the percentage of participants who achieved VGPR or complete response (CR) (including stringent complete response \[sCR\]) according to the IMWG criteria during or after the study treatment. VGPR: Serum and urine component detectable by immunofixation but not on electrophoresis, or \>= 90% reduction in serum M-protein plus urine M-protein level \<100 mg/24 hour; CR: negative immunofixation on the serum and urine, Disappearance of any soft tissue plasmacytomas and \<5% PCs in bone marrow; sCR: CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.

  Up to 2 years and 3 months

Secondary Outcomes (9)

• Maximum Observed Serum Concentration (Cmax) of Daratumumab

  D-VRd: Day 4 of Cycles 1 and 4 and post treatment at Week 8; D-VMP: Day 4 of Cycles 1 and 2 and post treatment at Week 8; D-Rd and D-Kd: Day 4 of Cycles 1 and 3 and post treatment at Week 8

• Percentage of Participants With Infusion-Related Reactions (IRRs)

  For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

• D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response

  From baseline up to 2 years 7 months

• D-VRd Cohort: Overall Response Rate (ORR)

  Up to 2 years and 3 months

• Percentage of Participants With CR or Better Response

  For D-VRD Arm: Baseline up to 2 years 3 months; For D-VMP, D-Rd and D-Kd Arms: Baseline up to 2 years 7 months

Study Arms (4)

Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

EXPERIMENTAL

Participants will receive daratumumab 1800 milligram (mg) by subcutaneous (SC) injection on Days 1, 8 and 15 of Cycles 1 to 3 (each cycle of 21 days) and on Day 1 of Cycle 4; bortezomib 1.3 milligram per square meter (mg/m\^2) SC injection on Days 1, 4, 8 and 11 of Cycles 1 to 4; lenalidomide 25 mg orally on Day 1 through Day 14 of Cycles 1 to 4 and dexamethasone 20 mg orally or intravenously on Days 1, 2 ,8, 9, 15 and 16 of Cycle 1 to 4.

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

D + Bortezomib + Melphalan + Prednisone (D-VMP)

EXPERIMENTAL

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15, 22, 29 and 36 of Cycle 1 then on Days 1 and 22 in Cycles 2 to 9 and Day 1 of Cycle 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; bortezomib 1.3 mg/m\^2 SC injection on Day 1, 4, 8, 11, 22, 25, 29 and 32 of Cycle 1 and on Days 1, 8, 22 and 29 of Cycles 2 to 9; melphalan 9 mg/m\^2 orally on Day 1 through Day 4 of Cycles 1 to 9; prednisone 60 mg/m\^2 orally on Days 1 to 4 of cycles 1 to 9.

Drug: Daratumumab; Drug: Bortezomib; Drug: Melphalan; Drug: Prednisone

Daratumumab + Lenalidomide + Dexamethasone (D-Rd)

EXPERIMENTAL

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; lenalidomide 25 mg orally on Day 1 through Day 21 of each cycle until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or intravenously weekly until documented progression of disease, unacceptable toxicity, or end of study.

Drug: Daratumumab; Drug: Lenalidomide; Drug: Dexamethasone

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

EXPERIMENTAL

Participants will receive daratumumab 1800 mg by SC injection on Days 1, 8, 15 and 22 of Cycles 1 and 2 (each cycle is of 28 days) then on Day 1 and 15 of Cycles 3 to 6 and on Day 1 of Cycle 7 and thereafter until documented progression of disease, unacceptable toxicity, or end of study; Carfilzomib 20 mg/m\^2 intravenously (IV) on Day 1 of Cycle 1 only then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study and dexamethasone 40 mg orally or IV weekly for Cycles 1-9 then on Days 1, 8, 15 of each cycle for Cycles 10 and thereafter until documented progression of disease, unacceptable toxicity, or end of study.

Drug: Daratumumab; Drug: Dexamethasone; Drug: Carfilzomib

Interventions

Daratumumab DRUG

Daratumumab will be administered at a dose of 1800 mg by SC injection in Cycles 1 to 4 in D-VRd cohort and until documented progression of disease, unacceptable toxicity, or end of study for D-VMP, D-Rd and D-Kd cohorts.

D + Bortezomib + Melphalan + Prednisone (D-VMP); Daratumumab + Carfilzomib + Dexamethasone (D-Kd); Daratumumab + Lenalidomide + Dexamethasone (D-Rd); Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Bortezomib DRUG

Bortezomib will be administered as 1.3 mg/m\^2 SC injection in Cycles 1 to 4 in D-VRd cohort and in Cycles 1 to 9 in D-VMP cohort.

D + Bortezomib + Melphalan + Prednisone (D-VMP); Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Lenalidomide DRUG

Lenalidomide will be administered as 25 mg capsule orally in Cycles 1 to 4 in D-VRd cohort and in all Cycles until documented progression of disease, unacceptable toxicity, or end of study in D-Rd cohort.

Daratumumab + Lenalidomide + Dexamethasone (D-Rd); Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Dexamethasone DRUG

Dexamethasone will be administered as 20 mg orally or intravenously in Cycles 1 to 4 in D-VRd cohort; 40 mg orally or intravenously in all cycles and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Rd and D-Kd cohort.

Daratumumab + Carfilzomib + Dexamethasone (D-Kd); Daratumumab + Lenalidomide + Dexamethasone (D-Rd); Daratumumab(D)+Bortezomib+Lenalidomide+Dexamethasone (D-VRd)

Melphalan DRUG

Melphalan will be administered as 9 mg/m\^2 orally in Cycles 1 to 9.

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Prednisone DRUG

Prednisone will be administered as 60 mg/m\^2 orally in cycles 1 to 9.

D + Bortezomib + Melphalan + Prednisone (D-VMP)

Carfilzomib DRUG

Carfilzomib will be administered as 20 mg/m\^2 IV on Day 1 of Cycle 1 only then 70 mg/m\^2 IV on Days 8 and 15 of Cycle 1 and Days 1, 8 and 15 of Cycle 2 and thereafter until documented progression of disease, unacceptable toxicity, or end of study in D-Kd cohort.

Daratumumab + Carfilzomib + Dexamethasone (D-Kd)

Eligibility Criteria

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

You may qualify if:

• Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
• Measurable, secretory disease as defined by any of the following:
• Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL); or
• Urine M-protein level \>= 200 milligram per 24 hours (mg/24 hours); or
• Light chain multiple myeloma (MM), for participants without measurable disease in the serum or urine: serum Immunoglobulin (Ig) free light chain (FLC) \>= 10 mg/dL and abnormal FLC ratio
• Meets one of the sets of the following criteria:
• For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma
• For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease
• D-Kd cohort: Participants must have received only 1 prior line of therapy for MM which included at least 2 consecutive cycles of lenalidomide therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0, 1, or 2
• During the study, during dose interruptions, and for 3 months after receiving the last dose of any component of the study treatment, a female participant must agree not to donate eggs (ova, oocytes) and male participants of reproductive potential must not donate semen or sperm during the study, during dose interruptions, or for 3 months after the last dose of any study drug

You may not qualify if:

• History of malignancy (other than MM) unless all treatment of that malignancy was completed at least 2 years before consent and the participant has no evidence of disease further exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years
• Exhibits clinical signs of meningeal involvement of MM
• Either of the following: a) Chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) is less than (\<) 50 percentage (%) of predicted normal b) Moderate or severe persistent asthma, or a history of asthma within the last 2 years, or currently has uncontrolled asthma of any classification c) For D-Kd cohort: Known infiltrative pulmonary disease or known pulmonary hypertension
• Any of the following: a) Known to be seropositive for human immunodeficiency virus; b) Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Participants with resolved infection (participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen \[Anti-HBc\] and/or antibodies to hepatitis B surface antigen \[Anti-HBs\]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are polymerase chain reaction (PCR) positive will be excluded
• Known to be seropositive for hepatitis C (Anti-HCV antibody positive or HCV-RNA quantitation positive) except in the setting of a sustained virologic response \[SVR\], defined as aviremia at least 12 weeks after completion of antiviral therapy
• For D-Kd cohort only: Transthoracic echocardiogram showing left ventricular ejection fraction (LVEF) \<40%; uncontrolled hypertension, defined as an average systolic blood pressure greater than (\>)159 millimeters of mercury (mmHg) or diastolic \>99 mmHg despite optimal treatment

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (64)

Cancer Center of Central Connecticut - Southington

Southington, Connecticut, 06489-3237, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Karmonos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Providence Cancer Center

Southfield, Michigan, 48075, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Nebraska Hematology and Oncology

Lincoln, Nebraska, 68506, United States

Location

Southeast Nebraska Cancer Center

Lincoln, Nebraska, 68510, United States

Location

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

NYU Winthrop

Mineola, New York, 11501, United States

Location

Mt. Sinai School of Medicine

New York, New York, 10029, United States

Location

Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Avera Medical Group - Oncology & Hematology

Sioux Falls, South Dakota, 57105, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84121, United States

Location

University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic

Charlottesville, Virginia, 22903, United States

Location

Liga Norte Riograndense Contra O Cancer

Natal, 59062 000, Brazil

Location

Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo

Passo Fundo, 99010-090, Brazil

Location

Ministerio da Saude Instituto Nacional do Cancer

Rio de Janeiro, 20230 130, Brazil

Location

Clinica Sao Germano

São Paulo, 01455 010, Brazil

Location

SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo

São Paulo, 04037-002, Brazil

Location

Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE

São Paulo, 04039-004, Brazil

Location

Fakultni nemocnice Brno

Brno, 625 00, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava, 70852, Czechia

Location

Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie

Prague, 128 08, Czechia

Location

CHU de Nantes hotel Dieu

Nantes, 44093, France

Location

CHU de Bordeaux - Hospital Haut-Leveque

Pessac, 33604, France

Location

Centre hospitalier Lyon-Sud

Pierre-Bénite, 69495, France

Location

CHU Bretonneau

Tours, 37044, France

Location

CHU Nancy Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Klinikum Chemnitz gGmbH

Chemnitz, 09113, Germany

Location

Universitaetsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,

Tübingen, 72076, Germany

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Galilee Medical Center

Nahariya, 22100, Israel

Location

Sheba Medical Center

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Kanazawa University Hospital

Kanazawa, 920 8641, Japan

Location

Matsuyama Red Cross Hospital

Matsuyama, 790-8524, Japan

Location

Nagoya City University Hospital

Nagoya, 467 8602, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

Inst. Cat. D'Oncologia-Badalona

Badalona, 08916, Spain

Location

Hosp Clinic de Barcelona

Barcelona, 08036, Spain

Location

Inst. Cat. Doncologia-H Duran I Reynals

Barcelona, 08908, Spain

Location

Hosp Univ Vall D Hebron

Barcelona, 8035, Spain

Location

Hosp. Gral. Univ. Gregorio Maranon

Madrid, 28007, Spain

Location

Clinica Univ. de Navarra

Madrid, 28027, Spain

Location

Hosp. Univ. Ramon Y Cajal

Madrid, 28034, Spain

Location

Hosp. Univ. 12 de Octubre

Madrid, 28041, Spain

Location

Hosp. Son Llatzer

Mallorca, 07198, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Hosp. Univ. Dr. Peset

Valencia, 46017, Spain

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5SS, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, BH7 7DW, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, CT1 3NG, United Kingdom

Location

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Related Publications (1)

• Moreau P, Chari A, Oriol A, Martinez-Lopez J, Haenel M, Touzeau C, Ailawadhi S, Besemer B, de la Rubia Comos J, Encinas C, Mateos MV, Salwender H, Rodriguez-Otero P, Hulin C, Karlin L, Sureda Balari A, Bargay J, Benboubker L, Rosinol L, Tarantolo S, Terebelo H, Yang S, Wang J, Nnane I, Qi M, Kosh M, Delioukina M, Goldschmidt H. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. Blood Cancer J. 2023 Mar 7;13(1):33. doi: 10.1038/s41408-023-00805-x. No abstract available.

  PMID: 36882409 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

daratumumab; Bortezomib; Lenalidomide; Dexamethasone; Melphalan; Prednisone; carfilzomib

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; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Pregnadienediols

Results Point of Contact

• Title: GLOBAL MEDICAL HEAD
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2018
• First Posted: January 26, 2018
• Study Start: April 26, 2018
• Primary Completion: August 12, 2020
• Study Completion: April 18, 2024
• Last Updated: April 29, 2025
• Results First Posted: January 12, 2022

Record last verified: 2025-04

Locations

DE (5); BR (6); ES (12); US (16); CZ (4); IL (6); FR (5); JP (4); GB (6)