Clinical trial NCT02616640: A Study to Determine Dose and Regimen of Durvalumab as Monotherapy or in Combination With Pomalidomide With or Without Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
Official title: A Phase IB Multicenter, Open-label Study To Determine The Recommended Dose And Regimen Of Durvalumab (MEDI4736) Either As Monotherapy or In Combination With Pomalidomide (POM) With Or Without Low-Dose Dexamethasone (DEX) In Subjects With Relapsed And Refractory Multiple Myeloma (RRMM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed
Refractory
MEDI4736
Durvalumab
Pomalidomide (POM)
Dexamethasone (DEX)
PD-L1
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2015-11-30
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, Phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with POM with or without low dose dex in subjects with RRMM. The study will consist of a dose-finding portion as well as a parallel dose-expansion portion to determine the optimal dose and regimen.

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.


Eligibility criteria: Inclusion Criteria:

* Has a confirmed diagnosis of active multiple myeloma and measurable disease.
* Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy
* Must have failed last line of treatment (refractory to last line of treatment).
* Must have achieved at least a stable disease (SD) for at least 1 cycle of treatment to at least 1 prior anti-myeloma regimen before developing Progressive disease (PD) (relapsed)
* Prior anti-myeloma treatments must have included a lenalidomide AND proteasome inhibitor alone or in combination.
* Has performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* The extramedullary plasmacytoma (EMP) sub-group, must have radiologically measurable EMP disease (soft tissue or bone related) that is amenable to biopsy and does not need to have measurable disease.

Exclusion Criteria:

* Has non-secretory or oligosecretory multiple myeloma
* Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1
* Has undergone prior organ or allogeneic hematopoetic stem cell transplantation
* Has received previous therapy with pomalidomide and did not achieve at least a stable disease
* Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), antiprogrammed death-ligand 2 (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 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
* Had rash ≥ Grade 3 during prior thalidomide, lenalidomide, or pomalidomide therapy
* Has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, POM, or dex
* Has peripheral neuropathy ≥ Grade 2
* Has a known additional malignancy that is progressing or requires active treatment (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
* 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
* Is a current smoker

Primary outcomes:
measure: Dose-limiting Toxicities (DLTs)
timeFrame: Approximately 1 month
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: Up to approximately 2 year
measure: Overall response rate (ORR)
timeFrame: Up to approximately 2 year
measure: Time to response (TTR)
timeFrame: Up to approximately 2 year
measure: Duration of response (DOR)
timeFrame: Up to approximately 2 year
measure: Pharmacokinetics- Cmax
timeFrame: Up to approximately 1 year
measure: Pharmacokinetics- AUC
timeFrame: Up to approximately 1 year
measure: Pharmacokinetics- Tmax
timeFrame: Up to approximately 1 year
measure: Pharmacokinetics- t1/2
timeFrame: Up to approximately 1 year
measure: Pharmacokinetics- CL/F
timeFrame: Up to approximately 1 year
measure: Pharmacokinetics- Vz/F
timeFrame: Up to approximately 1 year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Local Institution - 102
state: Maryland
city: Boston
country: United States
facility: Local Institution - 114
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 108
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 115
state: Massachusetts
city: New York
country: United States
facility: Local Institution - 105
state: New York
city: Charlotte
country: United States
facility: Local Institution - 106
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 110
state: Ohio
city: Milwaukee
country: United States
facility: Local Institution - 107
state: Wisconsin
city: Calgary
country: Canada
facility: Local Institution - 201
state: Alberta
city: Lille
country: France
facility: Local Institution - 601
city: Poitiers Cedex
country: France
facility: Local Institution - 602
city: Toulouse CEDEX 9
country: France
facility: Local Institution - 603
city: Tuebingen
country: Germany
facility: Local Institution - 301
city: Pavia 2
country: Italy
facility: Local Institution - 403
city: Rozzano (MI)
country: Italy
facility: Local Institution - 405
city: Torino
country: Italy
facility: Local Institution - 401
city: Amsterdam
country: Netherlands
facility: Local Institution - 702
city: Rotterdam
country: Netherlands
facility: Local Institution - 701
city: Barcelona
country: Spain
facility: Local Institution - 501
city: Madrid
country: Spain
facility: Local Institution - 504
city: Pamplona
country: Spain
facility: Local Institution - 502
city: Valencia
country: Spain
facility: Local Institution - 505
Study officials:
affiliation: Celgene Corporation
name: Lars Sternas, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Young MH, Pietz G, Whalen E, Copeland W, Thompson E, Fox BA, Newhall KJ. Immunomodulation by durvalumab and pomalidomide in patients with relapsed/refractory multiple myeloma. Sci Rep. 2021 Aug 12;11(1):16460. doi: 10.1038/s41598-021-95902-x.