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

NCT ID: NCT02616640

Last Updated: 2024-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

114 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-11

Study Completion Date

2024-07-30

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Durvalumab monotherapy

Intravenous (IV) durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Durvalumab + pomalidomide (POM)

IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle and Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Pomalidomide

Intervention Type DRUG

Durvalumab + pomalidomide (POM) + dexamethasone (dex)

IV durvalumab at assigned dose level (750, 1500, 2250, or 3000 mg) over 1 hour on day 1 of a 28-day cycle with Oral POM 4 mg/day on Days 1 to 21 of each 28-day treatment cycle and Oral dex 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Pomalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Interventions

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Durvalumab

Intervention Type DRUG

Pomalidomide

Intervention Type DRUG

Dexamethasone

Intervention Type DRUG

Other Intervention Names

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MEDI4736

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Celgene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Lars Sternas, MD, PhD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

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Local Institution - 102

Baltimore, Maryland, United States

Site Status

Local Institution - 114

Boston, Massachusetts, United States

Site Status

Local Institution - 108

Boston, Massachusetts, United States

Site Status

Local Institution - 115

Boston, Massachusetts, United States

Site Status

Local Institution - 105

New York, New York, United States

Site Status

Local Institution - 106

Charlotte, North Carolina, United States

Site Status

Local Institution - 110

Cleveland, Ohio, United States

Site Status

Local Institution - 107

Milwaukee, Wisconsin, United States

Site Status

Local Institution - 201

Calgary, Alberta, Canada

Site Status

Local Institution - 601

Lille, , France

Site Status

Local Institution - 602

Poitiers, , France

Site Status

Local Institution - 603

Toulouse, , France

Site Status

Local Institution - 301

Tübingen, , Germany

Site Status

Local Institution - 403

Pavia, , Italy

Site Status

Local Institution - 405

Rozzano (MI), , Italy

Site Status

Local Institution - 401

Torino, , Italy

Site Status

Local Institution - 702

Amsterdam, , Netherlands

Site Status

Local Institution - 701

Rotterdam, , Netherlands

Site Status

Local Institution - 501

Barcelona, , Spain

Site Status

Local Institution - 504

Madrid, , Spain

Site Status

Local Institution - 502

Pamplona, , Spain

Site Status

Local Institution - 505

Valencia, , Spain

Site Status

Countries

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United States Canada France Germany Italy Netherlands Spain

References

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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.

Reference Type DERIVED
PMID: 34385543 (View on PubMed)

Related Links

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Other Identifiers

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MEDI4736-MM-001

Identifier Type: -

Identifier Source: org_study_id

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