Clinical trial NCT02807454: A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma
Official title: A Phase 2, Multicenter, Open-label, Study to Determine the Safety and Efficacy for the Combination of Durvalumab (DURVA) and Daratumumab (DARA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Phase 2
Open-Label
Durvalumab
Daratumumab
Multiple Myeloma
Relapsed and Refractory (RRMM)
FUSION MM-003
PD-L1
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2016-06-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter study to confirm the safety and efficacy of durvalumab + daratumumab (D2) in subjects with relapsed and refractory multiple myeloma. This study will also explore the safety and efficacy of the addition of pomalidomide + dexamethasone to durvalumab + daratumumab (PD3).

On 05 Sep 2017, a Partial Clinical Hold was placed on this study by the United States (US) Food and Drug Administration (FDA). The decision by the FDA was based on data related to risks of anti-programmed cell death-1 (PD-1) antibody, pembrolizumab, in combination with IMiDs® immunomodulatory drugs in patients with multiple myeloma. As a result, enrollment into this study has been discontinued. Subjects who are receiving clinical benefit, based on the discretion of the investigator, may remain on study treatment after being reconsented.


Eligibility criteria: Inclusion Criteria:

* Must have measurable disease as defined by m-protein or serum free light chain.
* Must have failed last line of treatment (refractory to last line of treatment).
* Must have achieved at least a minimal response (MR) to at least 1 prior anti-myeloma regimen before developing PD (relapsed)
* Has performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Must be at least 18 years of age

Exclusion Criteria:

* Has non-secretory multiple myeloma
* Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1
* Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).
* Has received prior treatment with daratumumab or other anti-CD38 therapies previously
* Has undergone prior organ or allogeneic hematopoetic stem cell transplantation
* Has received autologous stem cell transplantation (ASCT) within 12 weeks before the date of randomization.
* Has received prior treatment with a monoclonal antibody within 5 half-lives of Study Day 1
* Has received investigational agents within 28 days or 5 half-lives (whichever is longer) of Study Day 1
* Has received live, attenuated vaccine within 30 days prior to Study Day 1
* Has chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal
* Has moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification.
* Is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C
* Has a prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years (with the exception Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer \[T1a or T1b\] or prostate cancer that is curative)
* Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma
* Has clinically significant cardiac disease
* Is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during the participation in the study

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From first dose to up to approximately 66 months
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From first dose to 90 days after last dose (up to approximately 58 months)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose to 90 days after last dose (up to approximately 58 months)
Secondary outcomes:
measure: Time-To-Response (TTR)
timeFrame: From enrollment to earliest documented response (up to approximately 66 months)
measure: Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm
timeFrame: From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
measure: Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm
timeFrame: From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
measure: Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm
timeFrame: From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
measure: Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm
timeFrame: From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
measure: Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm
timeFrame: Cycle 1 - Days 2, 8, 15, 22
measure: Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm
timeFrame: Cycle 1 - Days 2, 8, 15, 22
measure: Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm
timeFrame: Cycle 1 - Days 2, 8, 15, 22
measure: Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Simon Stage 1: D2 Arm
timeFrame: Cycle 1 - Days 2, 8, 15, 22
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Division of Hematology Oncology
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Denver
country: United States
facility: Local Institution - 007
state: Colorado
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Bethesda
country: United States
facility: Center For Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Partners Cancer Care, Inc.
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Philadelphia
country: United States
facility: Perelman Center for Advanced Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania - Perelman Center for Advanced Medicine
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology Nashville Drug Development Unit
state: Tennessee
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godine
city: Saint John
country: Canada
facility: Local Institution - 103
state: New Brunswick
city: Saint John
country: Canada
facility: Saint John Regional Hospital
state: New Brunswick
city: Toronto
country: Canada
facility: Local Institution - 104
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Local Institution - 101
state: Quebec
city: Montreal
country: Canada
facility: MUHC Glen Site
state: Quebec
city: Copenhagen
country: Denmark
facility: Local Institution - 552
city: Copenhagen
country: Denmark
facility: Rigshospitalet University Hospital
city: Odense
country: Denmark
facility: Local Institution - 553
city: Odense
country: Denmark
facility: Odense University Hospital
city: Vejle
country: Denmark
facility: Local Institution - 551
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus an der TU Dresden
city: Heidelberg
country: Germany
facility: Local Institution - 203
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
city: Tubingen
country: Germany
facility: University Hospital Tubingen
city: Wuerzburg
country: Germany
facility: Local Institution - 201
city: Wuerzburg
country: Germany
facility: Universitatsklinikum Wuerzburg
city: Bologna
country: Italy
facility: Local Institution - 354
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
city: Novara
country: Italy
facility: Local Institution - 353
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Padova
country: Italy
facility: Local Institution - 355
city: Palermo
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
city: Pisa
country: Italy
facility: A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia
city: Barcelona
country: Spain
facility: Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO
city: Barcelona
country: Spain
facility: Local Institution - 453
city: Gijon
country: Spain
facility: Hospital de Cabuenes
city: Gijon
country: Spain
facility: Local Institution - 451
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Local Institution - 452
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Lund
country: Sweden
facility: Local Institution - 501
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus Malmo
city: Stockholm
country: Sweden
facility: Local Institution - 502
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Huddinge
city: London
country: United Kingdom
facility: St. Bartholomew's and The Royal London Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Oxford
country: United Kingdom
facility: Local Institution - 252
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine
city: Sutton (Surrey)
country: United Kingdom
facility: Local Institution - 253
city: Sutton (Surrey)
country: United Kingdom
facility: Royal Marsden Hospital
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton Hospital NHS Trust
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: