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

NCT02807454 | Terminated Phase 2 Results

• 1 other identifier: MEDI4736-MM-003
• Study Type: interventional
• Target: 37
• Locations: 9 countries
• Sites: 64

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.

Conditions

Multiple Myeloma

Keywords

Phase 2; Open-Label; Durvalumab; Daratumumab; Multiple Myeloma; Relapsed and Refractory (RRMM); FUSION MM-003; PD-L1

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate (ORR)

  Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. ORR was calculated as the percent of responders (multiplied by 100). Partial response required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by ≥ 90% or to \< 200 mg per 24 hours.

  From first dose to up to approximately 66 months

• Number of Participants With Adverse Events (AEs)

  Number of participants who experienced at least one adverse event. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition should be considered an AE.

  From first dose to 90 days after last dose (up to approximately 58 months)

• Number of Participants With Serious Adverse Events (SAEs)

  Number of participants who experienced at least one serious adverse event. An SAE is any AE occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, constitutes an important medical event.

  From first dose to 90 days after last dose (up to approximately 58 months)

Secondary Outcomes (9)

• Time-To-Response (TTR)

  From enrollment to earliest documented response (up to approximately 66 months)

• Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm

  From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)

• Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm

  From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)

• Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm

  From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)

• Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm

  From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)

Study Arms (2)

Daratumumab Plus Durvalumab Treatment

EXPERIMENTAL

* 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

Drug: Daratumumab; Drug: Durvalumab

Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

EXPERIMENTAL

* 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

Drug: Daratumumab; Drug: Durvalumab; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Daratumumab DRUG

Daratumumab Plus Durvalumab Treatment; Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

Durvalumab DRUG

Daratumumab Plus Durvalumab Treatment; Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

Pomalidomide DRUG

Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

Dexamethasone DRUG

Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (64)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

UCLA Division of Hematology Oncology

Los Angeles, California, 90095-1752, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Local Institution - 007

Denver, Colorado, 80218, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Center For Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Dana-Farber Partners Cancer Care, Inc.

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology Nashville Drug Development Unit

Nashville, Tennessee, 37203, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven

Leuven, B-3000, Belgium

Location

Cliniques Universitaires UCL de Mont-Godine

Yvoir, 5530, Belgium

Location

Local Institution - 103

Saint John, New Brunswick, E2L 3L6, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 3L6, Canada

Location

Local Institution - 104

Toronto, Ontario, M5G 2M9, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

Local Institution - 101

Montreal, Quebec, H1T 2M4, Canada

Location

MUHC Glen Site

Montreal, Quebec, H4A 3J1, Canada

Location

Local Institution - 552

Copenhagen, 2100, Denmark

Location

Rigshospitalet University Hospital

Copenhagen, 2100, Denmark

Location

Local Institution - 553

Odense, DK-5000, Denmark

Location

Odense University Hospital

Odense, DK-5000, Denmark

Location

Local Institution - 551

Vejle, 7100, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Universitatsklinikum Carl Gustav Carus an der TU Dresden

Dresden, 01307, Germany

Location

Local Institution - 203

Heidelberg, 69115, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, 69115, Germany

Location

University Hospital Tubingen

Tübingen, 72076, Germany

Location

Local Institution - 201

Würzburg, 97080, Germany

Location

Universitatsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Local Institution - 354

Bologna, 40138, Italy

Location

Policlinico S. Orsola - Malpighi

Bologna, 40138, Italy

Location

A.O.U. Maggiore della Carità

Novara, 28100, Italy

Location

Local Institution - 353

Novara, 28100, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Local Institution - 355

Padua, 35128, Italy

Location

Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

Palermo, 90146, Italy

Location

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

Pisa, 56126, Italy

Location

Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO

Barcelona, 08907, Spain

Location

Local Institution - 453

Barcelona, 08907, Spain

Location

Hospital de Cabuenes

Gijón, 33394, Spain

Location

Local Institution - 451

Gijón, 33394, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Local Institution - 452

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Sahlgrenska University Hospital

Gothenburg, 60 Gothenburg, Sweden

Location

Local Institution - 501

Lund, 221 85, Sweden

Location

Skanes Universitetssjukhus Malmo

Lund, 221 85, Sweden

Location

Local Institution - 502

Stockholm, SE-141 86, Sweden

Location

Karolinska Universitetssjukhuset - Huddinge

Stockholm, SE-14186, Sweden

Location

St. Bartholomew's and The Royal London Hospital

London, EC1A 7BE, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Local Institution - 252

Oxford, 0X3 7LE, United Kingdom

Location

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

Oxford, 0X3 7LE, United Kingdom

Location

Local Institution - 253

Sutton (Surrey), SM2 5PT, United Kingdom

Location

Royal Marsden Hospital

Sutton (Surrey), SM2 5PT, United Kingdom

Location

The Royal Wolverhampton Hospital NHS Trust

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

daratumumab; durvalumab; pomalidomide; 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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

This study stopped enrolling participants on 05-Sep-2017 and was terminated earlier than planned on 03-Jan-2022. This results disclosure report provides outputs from the Simon Stage 1: D2 and PD3 arms. Simon Stage 2: D2 did not enroll any participants.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please Email:

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 21, 2016
• Study Start: July 7, 2016
• Primary Completion: January 3, 2022
• Study Completion: January 3, 2022
• Last Updated: February 21, 2023
• Results First Posted: February 21, 2023

Record last verified: 2023-02

Locations

ES (7); US (15); IT (8); DE (6); CA (7); SE (5); BE (3); DK (6); GB (7)