Clinical trial NCT03412565: A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Official title: A Multicenter Phase 2 Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2018-01-26
Enrollment: 265
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The hypothesis is that the addition of daratumumab administered SC to standard MM regimens will improve responses compared to response data observed in completed phase 3 studies without daratumumab. Disease evaluations will include measurements of myeloma proteins, bone marrow examinations, skeletal surveys, assessment of extramedullary plasmacytomas, and measurements of serum calcium corrected for albumin. Safety will be measured by adverse events, laboratory test results, electrocardiogram (ECGs), vital sign measurements, physical examination findings, SC injection-site assessments, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status score. Study will consist of 3 phases (screening, treatment and follow-up) and duration of study is approximately 3 years.

Eligibility criteria: Inclusion Criteria:

* Multiple myeloma diagnosed according to the International Myeloma Working Group (IMWG) diagnostic criteria
* Measurable, secretory disease as defined by any of the following:

  1. Serum monoclonal paraprotein (M-protein) level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL); or
  2. Urine M-protein level \>= 200 milligram per 24 hours (mg/24 hours); or
  3. 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:

  1. For Daratumumab + bortezomib + lenalidomide + dexamethasone (D-VRd) and Daratumumab + bortezomib + melphalan + prednisone + dexamethasone (D-VMP) regimen: newly diagnosed myeloma
  2. For Daratumumab + lenalidomide + dexamethasone (D-Rd) and Daratumumab + Carfilzomib + Dexamethasone (D-Kd) regimen: relapsed or refractory disease
  3. 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: D-VMP, D-Rd, and D-Kd Cohorts: Overall Response Rate (ORR)
timeFrame: Up to 2 years 3 months
measure: D-VRd Cohort: Percentage of Participants With Very Good Partial Response (VGPR) or Better Response
timeFrame: Up to 2 years and 3 months
Secondary outcomes:
measure: Maximum Observed Serum Concentration (Cmax) of Daratumumab
timeFrame: 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
measure: Percentage of Participants With Infusion-Related Reactions (IRRs)
timeFrame: 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
measure: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With VGPR or Better Response
timeFrame: From baseline up to 2 years 7 months
measure: D-VRd Cohort: Overall Response Rate (ORR)
timeFrame: Up to 2 years and 3 months
measure: Percentage of Participants With CR or Better Response
timeFrame: 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
measure: D-VMP, D-Rd and D-Kd Cohorts: Duration of Response (DOR)
timeFrame: From baseline up to 2 years 7 months
measure: Percentage of Participants With Anti-Daratumumab Antibodies
timeFrame: 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
measure: Percentage of Participants With Anti-rHuPH20 Antibodies
timeFrame: 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
measure: D-VMP, D-Rd, and D-Kd Cohorts: Percentage of Participants With Minimal Residual Disease (MRD) Negative Rate
timeFrame: Up to 2 years and 3 months
Other outcomes:
Locations:
city: Southington
country: United States
facility: Cancer Center of Central Connecticut - Southington
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Detroit
country: United States
facility: Karmonos Cancer Institute
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Center
state: Michigan
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Lincoln
country: United States
facility: Nebraska Hematology and Oncology
state: Nebraska
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Mineola
country: United States
facility: NYU Winthrop
state: New York
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Baptist Medical Center (WFUBMC) - Comprehensive Cancer Center
state: North Carolina
city: Sioux Falls
country: United States
facility: Avera Medical Group - Oncology & Hematology
state: South Dakota
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center - Emily Couric Clinical Cancer Center - Women's Oncology Clinic
state: Virginia
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Passo Fundo
country: Brazil
facility: Associacao Hospitalar Beneficente Sao Vicente de Paulo - Hospital Sao Vicente de Paulo
city: Rio de Janeiro
country: Brazil
facility: Ministerio da Saude Instituto Nacional do Cancer
city: Sao Paulo
country: Brazil
facility: SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto de Assistencia Medica ao Servidor Publico Estadual IAMSPE
city: São Paulo
country: Brazil
facility: Clinica Sao Germano
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze - I. interni klinika - klinika hematologie
city: Nantes Cedex 1
country: France
facility: CHU de Nantes hotel Dieu
city: Pessac cedex
country: France
facility: CHU de Bordeaux - Hospital Haut-Leveque
city: Pierre-Bénite
country: France
facility: Centre hospitalier Lyon-Sud
city: Tours Cedex 9
country: France
facility: CHU Bretonneau
city: Vandoeuvre Les Nancy
country: France
facility: CHU Nancy Brabois
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Tübingen
country: Germany
facility: Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel-Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
city: Matsuyama
country: Japan
facility: Matsuyama Red Cross Hospital
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
city: Badalona
country: Spain
facility: Inst. Cat. D'Oncologia-Badalona
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Clinica Univ. de Navarra
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Mallorca
country: Spain
facility: Hosp. Son Llatzer
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Valencia
country: Spain
facility: Hosp. Univ. Dr. Peset
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Stoke on Trent
country: United Kingdom
facility: Royal Stoke University Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: