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A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma (FUSIONMM-003)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02807454
Recruitment Status : Active, not recruiting
First Posted : June 21, 2016
Last Update Posted : January 31, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE June 17, 2016
First Posted Date  ICMJE June 21, 2016
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE July 7, 2016
Estimated Primary Completion Date July 5, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
  • Overall Response Rate (ORR) [ Time Frame: Up to approximately 1.5 years ]
    Defined as tumor response (including progressive disease), based on the investigator assessments according to the International Myeloma Working Group (IMWG) Uniform Response Criteria
  • Adverse Events (AEs) [ Time Frame: Up to approximately 1.5 years ]
    Number of participants with adverse events
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
  • Time to response (TTR) [ Time Frame: up to approximately 1.5 years ]
    Time from enrollment to the first documentation of response (Partial Response [PR] or greater)
  • Duration of Response (DOR) [ Time Frame: up to approximately 2.5 years ]
    Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)
  • Progression-free Survival (PFS) [ Time Frame: up to approximately 2 years ]
    Time from enrollment to the first documentation of PD or death from any cause during study, whichever occurs earlier
  • Pharmacokinetics- Cmax [ Time Frame: up to approximately 2 years ]
    Maximum observed concentration
  • Pharmacokinetics- AUC [ Time Frame: up to approximately 2 years ]
    Area under the concentration-time curve
  • Pharmacokinetics- Tmax [ Time Frame: up to approximately 2 years ]
    Time to maximum concentration
  • Pharmacokinetics- t1/2 [ Time Frame: up to approximately 2 years ]
    Terminal elimination half-life
  • Pharmacokinetics- CL/F [ Time Frame: up to approximately 2 years ]
    Apparent total body clearance
  • Pharmacokinetics- Vz/F [ Time Frame: up to approximately 2 years ]
    Apparent volume of distribution
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma
Official Title  ICMJE 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)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Daratumumab
  • Drug: Durvalumab
  • Drug: Pomalidomide
  • Drug: Dexamethasone
Study Arms  ICMJE
  • Experimental: 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
    Interventions:
    • Drug: Daratumumab
    • Drug: Durvalumab
  • Experimental: 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
    Interventions:
    • Drug: Daratumumab
    • Drug: Durvalumab
    • Drug: Pomalidomide
    • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 7, 2018)
37
Original Estimated Enrollment  ICMJE
 (submitted: June 17, 2016)
144
Estimated Study Completion Date  ICMJE July 5, 2020
Estimated Primary Completion Date July 5, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Denmark,   Germany,   Italy,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02807454
Other Study ID Numbers  ICMJE MEDI4736-MM-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Celgene
Study Sponsor  ICMJE Celgene
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Lars Sternas, MD, PhD Celgene Corporation
Study Director: Teresa Peluso, MBBS, DCPSA Celgene
PRS Account Celgene
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP