A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma

NCT ID: NCT02807454

Last Updated: 2023-02-21

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-07

Study Completion Date

2022-01-03

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Daratumumab Plus Durvalumab Treatment

* Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle
* IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Durvalumab

Intervention Type DRUG

Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

* Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle
* IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward
* oral POM at 4mg/day on days 1 to 21
* oral/IV dex at 40mg/day (\>75 years old) or 20mg/day (\>75 years old) on days 1, 8, 15 and 22

Group Type EXPERIMENTAL

Daratumumab

Intervention Type DRUG

Durvalumab

Intervention Type DRUG

Pomalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Interventions

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Daratumumab

Intervention Type DRUG

Durvalumab

Intervention Type DRUG

Pomalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

UCLA Division of Hematology Oncology

Los Angeles, California, United States

Site Status

Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status

Local Institution - 007

Denver, Colorado, United States

Site Status

Emory University Hospital

Atlanta, Georgia, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Center For Cancer and Blood Disorders

Bethesda, Maryland, United States

Site Status

Dana-Farber Partners Cancer Care, Inc.

Boston, Massachusetts, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status

Tennessee Oncology Nashville Drug Development Unit

Nashville, Tennessee, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

AZ St-Jan Brugge Oostende AV

Bruges, , Belgium

Site Status

Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven

Leuven, , Belgium

Site Status

Cliniques Universitaires UCL de Mont-Godine

Yvoir, , Belgium

Site Status

Local Institution - 103

Saint John, New Brunswick, Canada

Site Status

Saint John Regional Hospital

Saint John, New Brunswick, Canada

Site Status

Local Institution - 104

Toronto, Ontario, Canada

Site Status

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Site Status

Local Institution - 101

Montreal, Quebec, Canada

Site Status

MUHC Glen Site

Montreal, Quebec, Canada

Site Status

Local Institution - 552

Copenhagen, , Denmark

Site Status

Rigshospitalet University Hospital

Copenhagen, , Denmark

Site Status

Local Institution - 553

Odense, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Local Institution - 551

Vejle, , Denmark

Site Status

Vejle Hospital

Vejle, , Denmark

Site Status

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, , Germany

Site Status

Local Institution - 203

Heidelberg, , Germany

Site Status

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Site Status

University Hospital Tubingen

Tübingen, , Germany

Site Status

Local Institution - 201

Würzburg, , Germany

Site Status

Universitatsklinikum Wuerzburg

Würzburg, , Germany

Site Status

Local Institution - 354

Bologna, , Italy

Site Status

Policlinico S. Orsola - Malpighi

Bologna, , Italy

Site Status

A.O.U. Maggiore della Carità

Novara, , Italy

Site Status

Local Institution - 353

Novara, , Italy

Site Status

Azienda Ospedaliera di Padova

Padua, , Italy

Site Status

Local Institution - 355

Padua, , Italy

Site Status

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, , Italy

Site Status

A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia

Pisa, , Italy

Site Status

Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO

Barcelona, , Spain

Site Status

Local Institution - 453

Barcelona, , Spain

Site Status

Hospital de Cabuenes

Gijón, , Spain

Site Status

Local Institution - 451

Gijón, , Spain

Site Status

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Local Institution - 452

Madrid, , Spain

Site Status

Hospital 12 de Octubre

Madrid, , Spain

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Local Institution - 501

Lund, , Sweden

Site Status

Skanes Universitetssjukhus Malmo

Lund, , Sweden

Site Status

Local Institution - 502

Stockholm, , Sweden

Site Status

Karolinska Universitetssjukhuset - Huddinge

Stockholm, , Sweden

Site Status

St. Bartholomew's and The Royal London Hospital

London, , United Kingdom

Site Status

Christie Hospital

Manchester, , United Kingdom

Site Status

Local Institution - 252

Oxford, , United Kingdom

Site Status

Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine

Oxford, , United Kingdom

Site Status

Local Institution - 253

Sutton (Surrey), , United Kingdom

Site Status

Royal Marsden Hospital

Sutton (Surrey), , United Kingdom

Site Status

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, , United Kingdom

Site Status

Countries

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United States Belgium Canada Denmark Germany Italy Spain Sweden United Kingdom

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MEDI4736-MM-003

Identifier Type: -

Identifier Source: org_study_id

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