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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)

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ClinicalTrials.gov Identifier: NCT02807454
Recruitment Status : Active, not recruiting
First Posted : June 21, 2016
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Description
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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.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: Durvalumab Drug: Pomalidomide Drug: Dexamethasone Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 7, 2016
Estimated Primary Completion Date : July 8, 2019
Estimated Study Completion Date : July 8, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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Arm Intervention/treatment
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
 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
 Drug: Daratumumab
Drug: Durvalumab
Drug: Pomalidomide
Drug: Dexamethasone


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. Adverse Events (AEs) [ Time Frame: Up to approximately 1.5 years ]
    Number of participants with adverse events


Secondary Outcome Measures :
  1. 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)

  2. 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)

  3. 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

  4. Pharmacokinetics- Cmax [ Time Frame: up to approximately 2 years ]
    Maximum observed concentration

  5. Pharmacokinetics- AUC [ Time Frame: up to approximately 2 years ]
    Area under the concentration-time curve

  6. Pharmacokinetics- Tmax [ Time Frame: up to approximately 2 years ]
    Time to maximum concentration

  7. Pharmacokinetics- t1/2 [ Time Frame: up to approximately 2 years ]
    Terminal elimination half-life

  8. Pharmacokinetics- CL/F [ Time Frame: up to approximately 2 years ]
    Apparent total body clearance

  9. Pharmacokinetics- Vz/F [ Time Frame: up to approximately 2 years ]
    Apparent volume of distribution


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02807454


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Sponsors and Collaborators
Celgene
Investigators
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Study Director: Lars Sternas, MD, PhD Celgene Corporation
Study Director: Teresa Peluso, MBBS, DCPSA Celgene
More Information
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02807454     History of Changes
Other Study ID Numbers: MEDI4736-MM-003
First Posted: June 21, 2016    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019

Keywords provided by Celgene:
Phase 2
Open-Label
Durvalumab
Daratumumab
 Multiple Myeloma
Relapsed and Refractory (RRMM)
FUSION MM-003
PD-L1

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
 Dexamethasone acetate
Durvalumab
Pomalidomide
Daratumumab
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists