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

NCT02616640 | Completed Phase 1

• 1 other identifier: MEDI4736-MM-001
• Study Type: interventional
• Target: 114
• Locations: 7 countries
• Sites: 22

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed; Refractory; MEDI4736; Durvalumab; Pomalidomide (POM); Dexamethasone (DEX); PD-L1

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicities (DLTs)

  Number of participants with DLTs in the first cycle of treatment

  Approximately 1 month

Secondary Outcomes (10)

• Adverse Events (AEs)

  Up to approximately 2 year

• Overall response rate (ORR)

  Up to approximately 2 year

• Time to response (TTR)

  Up to approximately 2 year

• Duration of response (DOR)

  Up to approximately 2 year

• Pharmacokinetics- Cmax

  Up to approximately 1 year

Study Arms (3)

Durvalumab monotherapy

EXPERIMENTAL

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

Drug: Durvalumab

Durvalumab + pomalidomide (POM)

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Pomalidomide

Durvalumab + pomalidomide (POM) + dexamethasone (dex)

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Durvalumab DRUG

Also known as: MEDI4736

Durvalumab + pomalidomide (POM); Durvalumab + pomalidomide (POM) + dexamethasone (dex); Durvalumab monotherapy

Pomalidomide DRUG

Durvalumab + pomalidomide (POM); Durvalumab + pomalidomide (POM) + dexamethasone (dex)

Dexamethasone DRUG

Durvalumab + pomalidomide (POM) + dexamethasone (dex)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (22)

Local Institution - 102

Baltimore, Maryland, 21231, United States

Location

Local Institution - 114

Boston, Massachusetts, 02114, United States

Location

Local Institution - 108

Boston, Massachusetts, 02115, United States

Location

Local Institution - 115

Boston, Massachusetts, 02215, United States

Location

Local Institution - 105

New York, New York, 10065, United States

Location

Local Institution - 106

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 110

Cleveland, Ohio, 44195, United States

Location

Local Institution - 107

Milwaukee, Wisconsin, 53226, United States

Location

Local Institution - 201

Calgary, Alberta, T2N 4N2, Canada

Location

Local Institution - 601

Lille, 59037, France

Location

Local Institution - 602

Poitiers, 86021, France

Location

Local Institution - 603

Toulouse, 31059, France

Location

Local Institution - 301

Tübingen, 72076, Germany

Location

Local Institution - 403

Pavia, 27100, Italy

Location

Local Institution - 405

Rozzano (MI), 20089, Italy

Location

Local Institution - 401

Torino, 10126, Italy

Location

Local Institution - 702

Amsterdam, 1081 HV, Netherlands

Location

Local Institution - 701

Rotterdam, 3015 CN, Netherlands

Location

Local Institution - 501

Barcelona, 08916, Spain

Location

Local Institution - 504

Madrid, 28041, Spain

Location

Local Institution - 502

Pamplona, 31008, Spain

Location

Local Institution - 505

Valencia, 46026, Spain

Location

Related Publications (1)

• 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.

  PMID: 34385543 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

durvalumab; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Lars Sternas, MD, PhD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 25, 2015
• First Posted: November 30, 2015
• Study Start: January 11, 2016
• Primary Completion: November 23, 2018
• Study Completion: July 30, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-08

Locations

IT (3); CA (1); DE (1); NL (2); ES (4); FR (3); US (8)