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Multiple MyelomaPhase 2FUSIONMM-003NCT02807454

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

A Phase 2 study testing Daratumumab, Durvalumab and Pomalidomide in people with Multiple Myeloma, run by Celgene at 64 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Daratumumab, Durvalumab and Pomalidomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
64 sitesin 9 countries
Study dates
7 Jul 2016to 3 Jan 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 16Show fewer
  • 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

Trial locations and contacts

64 sites in 9 countries.

64 sites in 9 countries

United States15 sites

  • Emory University Hospital

    Atlanta, Georgia, 30322

  • Center For Cancer and Blood Disorders

    Bethesda, Maryland, 20817

  • Dana-Farber Partners Cancer Care, Inc.

    Boston, Massachusetts, 02115

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • Local Institution - 007

    Denver, Colorado, 80218

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • UCLA Division of Hematology Oncology

    Los Angeles, California, 90095-1752

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Tennessee Oncology Nashville Drug Development Unit

    Nashville, Tennessee, 37203

  • Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • University of Pennsylvania - Perelman Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • Swedish Medical Center

    Seattle, Washington, 98104

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Italy8 sites

  • Local Institution - 354

    Bologna, 40138

  • Policlinico S. Orsola - Malpighi

    Bologna, 40138

  • A.O.U. Maggiore della Carità

    Novara, 28100

  • Local Institution - 353

    Novara, 28100

  • Azienda Ospedaliera di Padova

    Padova, 35128

  • Local Institution - 355

    Padova, 35128

  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello

    Palermo, 90146

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

    Pisa, 56126

Other trials in Italy

Canada7 sites

  • Hopital Maisonneuve-Rosemont

    Montreal, Quebec, H1T 2M4

  • Local Institution - 101

    Montreal, Quebec, H1T 2M4

  • MUHC Glen Site

    Montreal, Quebec, H4A 3J1

  • Local Institution - 103

    Saint John, New Brunswick, E2L 3L6

  • Saint John Regional Hospital

    Saint John, New Brunswick, E2L 3L6

  • Local Institution - 104

    Toronto, Ontario, M5G 2M9

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Spain7 sites

  • Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO

    Barcelona, 08907

  • Local Institution - 453

    Barcelona, 08907

  • Hospital de Cabuenes

    Gijón, 33394

  • Local Institution - 451

    Gijón, 33394

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • Local Institution - 452

    Madrid, 28040

  • Hospital 12 de Octubre

    Madrid, 28041

Other trials in Spain

United Kingdom7 sites

  • St. Bartholomew's and The Royal London Hospital

    London, EC1A 7BE

  • Christie Hospital

    Manchester, M20 4BX

  • Local Institution - 252

    Oxford, 0X3 7LE

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

    Oxford, 0X3 7LE

  • Local Institution - 253

    Sutton (Surrey), SM2 5PT

  • Royal Marsden Hospital

    Sutton (Surrey), SM2 5PT

  • The Royal Wolverhampton Hospital NHS Trust

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Denmark6 sites

  • Local Institution - 552

    Copenhagen, 2100

  • Rigshospitalet University Hospital

    Copenhagen, 2100

  • Local Institution - 553

    Odense, DK-5000

  • Odense University Hospital

    Odense, DK-5000

  • Local Institution - 551

    Vejle, 7100

  • Vejle Hospital

    Vejle, 7100

Other trials in Denmark

Germany6 sites

  • Universitatsklinikum Carl Gustav Carus an der TU Dresden

    Dresden, 01307

  • Local Institution - 203

    Heidelberg, 69115

  • Universitatsklinikum Heidelberg

    Heidelberg, 69115

  • University Hospital Tubingen

    Tübingen, 72076

  • Local Institution - 201

    Würzburg, 97080

  • Universitatsklinikum Wuerzburg

    Würzburg, 97080

Other trials in Germany

Sweden5 sites

  • Sahlgrenska University Hospital

    Gothenburg, 60 Gothenburg

  • Local Institution - 501

    Lund, 221 85

  • Skanes Universitetssjukhus Malmo

    Lund, 221 85

  • Local Institution - 502

    Stockholm, SE-141 86

  • Karolinska Universitetssjukhuset - Huddinge

    Stockholm, SE-14186

Other trials in Sweden

Belgium3 sites

  • AZ St-Jan Brugge Oostende AV

    Bruges, 8000

  • Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven

    Leuven, B-3000

  • Cliniques Universitaires UCL de Mont-Godine

    Yvoir, 5530

Other trials in Belgium

About this study

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)

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.

Keywords
Phase 2, Open-Label, Durvalumab, Daratumumab, Multiple Myeloma, Relapsed and Refractory (RRMM), FUSION MM-003, PD-L1
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02807454
Study groupRoleWhat they receive
Daratumumab Plus Durvalumab TreatmentExperimental* 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
Receives: Drug: Daratumumab; Drug: Durvalumab
Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone TreatmentExperimental* 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
Receives: Drug: Daratumumab; Drug: Durvalumab; Drug: Pomalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From first dose to up to approximately 66 months

  2. 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.

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

  3. 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.

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

Secondary outcomes (9)

  1. Time-To-Response (TTR)

    Time-to-response is calculated as the time from enrollment to the first date of documented response (partial response or better). Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. 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. For those participants where POM + DEX were added, time-to-response was calculated from the date POM and DEX were added to the first date of documented response (PR or better).

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

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

    Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. 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. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h).

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

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

    Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease progression as determined by the investigator. Participants who are alive or lost to follow-up will be censored on the last-known-to-be-alive date. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. 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.

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

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

    Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h).

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

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

    Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (absolute increase must be ≥ 200 mg/24 h).

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

  6. Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm

    Pharmacokinetics of Durvalumab derived from serum concentration versus time data.

    Measured: Cycle 1 - Days 2, 8, 15, 22

  7. Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm

    Pharmacokinetics of Durvalumab derived from serum concentration versus time data.

    Measured: Cycle 1 - Days 2, 8, 15, 22

  8. Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm

    Pharmacokinetics of Durvalumab derived from serum concentration versus time data.

    Measured: Cycle 1 - Days 2, 8, 15, 22

  9. Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Simon Stage 1: D2 Arm

    Pharmacokinetics of Durvalumab derived from serum concentration versus time data.

    Measured: Cycle 1 - Days 2, 8, 15, 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2016 (estimated)
  2. Study start7 Jul 2016
  3. Primary completion3 Jan 2022
  4. Study completion3 Jan 2022

Why it stopped: Health Authority request due to class effect

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02807454
Sponsor's protocol ID
MEDI4736-MM-003
Acronym
FUSIONMM-003
Status last verified
Feb 2023
First submitted
17 Jun 2016
Last updated
21 Feb 2023
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Durvalumab and Pomalidomide in people with Multiple Myeloma, run by Celgene at 64 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Italy, Canada, Spain, United Kingdom and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: From first dose to up to approximately 66 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02807454.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.

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