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

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02616640
• Other study ID #: MEDI4736-MM-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 11, 2016
• Est. completion date: April 9, 2024

Study information

• Verified date: March 2024
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 114
• Est. completion date: April 9, 2024
• Est. primary completion date: November 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Durvalumab

• Pomalidomide

• Dexamethasone

Locations

Country	Name	City	State
Canada	Local Institution - 201	Calgary	Alberta
France	Local Institution - 601	Lille
France	Local Institution - 602	Poitiers Cedex
France	Local Institution - 603	Toulouse CEDEX 9
Germany	Local Institution - 301	Tuebingen
Italy	Local Institution - 403	Pavia 2
Italy	Local Institution - 405	Rozzano (MI)
Italy	Local Institution - 401	Torino
Netherlands	Local Institution - 702	Amsterdam
Netherlands	Local Institution - 701	Rotterdam
Spain	Local Institution - 501	Barcelona
Spain	Local Institution - 504	Madrid
Spain	Local Institution - 502	Pamplona
Spain	Local Institution - 505	Valencia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Local Institution - 108	Boston	Massachusetts
United States	Local Institution - 114	Boston	Massachusetts
United States	Local Institution - 115	Boston	Massachusetts
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Froedtert Hospital BMT Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Weill Medical College Of Cornell University	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting Toxicities (DLTs)	Number of participants with DLTs in the first cycle of treatment	Approximately 1 month
Secondary	Adverse Events (AEs)	Number of participants with adverse events	Up to approximately 2 year
Secondary	Overall response rate (ORR)	Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria	Up to approximately 2 year
Secondary	Time to response (TTR)	Time from first dose to the first documentation of response (Partial Response [PR] or greater)	Up to approximately 2 year
Secondary	Duration of response (DOR)	Is defined as time from the earliest date of documented response (partial response (PR) or better) to the earliest date when disease progression was confirmed	Up to approximately 2 year
Secondary	Pharmacokinetics- Cmax	Maximum observed concentration	Up to approximately 1 year
Secondary	Pharmacokinetics- AUC	Area under the concentration-time curve	Up to approximately 1 year
Secondary	Pharmacokinetics- Tmax	Time to maximum concentration	Up to approximately 1 year
Secondary	Pharmacokinetics- t1/2	Terminal elimination half-life	Up to approximately 1 year
Secondary	Pharmacokinetics- CL/F	Apparent total body clearance	Up to approximately 1 year
Secondary	Pharmacokinetics- Vz/F	Volume of distribution	Up to approximately 1 year

External Links

•   BMS Clinical Trial Information