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
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|ClinicalTrials.gov Identifier: NCT02616640|
Recruitment Status : Active, not recruiting
First Posted : November 30, 2015
Last Update Posted : April 27, 2023
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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.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Myeloma||Drug: Durvalumab Drug: Pomalidomide Drug: Dexamethasone||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||114 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||January 11, 2016|
|Actual Primary Completion Date :||January 10, 2017|
|Estimated Study Completion Date :||February 5, 2024|
Experimental: 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
Other Name: MEDI4736
Experimental: 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
Other Name: MEDI4736
Experimental: 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
Other Name: MEDI4736
- Dose-limiting Toxicities (DLTs) [ Time Frame: Approximately 1 month ]Number of participants with DLTs in the first cycle of treatment
- Adverse Events (AEs) [ Time Frame: Up to approximately 2 year ]Number of participants with adverse events
- Overall response rate (ORR) [ Time Frame: Up to approximately 2 year ]Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria
- Time to response (TTR) [ Time Frame: Up to approximately 2 year ]Time from first dose to the first documentation of response (Partial Response [PR] or greater)
- Duration of response (DOR) [ Time Frame: Up to approximately 2 year ]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
- Pharmacokinetics- Cmax [ Time Frame: Up to approximately 1 year ]Maximum observed concentration
- Pharmacokinetics- AUC [ Time Frame: Up to approximately 1 year ]Area under the concentration-time curve
- Pharmacokinetics- Tmax [ Time Frame: Up to approximately 1 year ]Time to maximum concentration
- Pharmacokinetics- t1/2 [ Time Frame: Up to approximately 1 year ]Terminal elimination half-life
- Pharmacokinetics- CL/F [ Time Frame: Up to approximately 1 year ]Apparent total body clearance
- Pharmacokinetics- Vz/F [ Time Frame: Up to approximately 1 year ]Volume of distribution
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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
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): NCT02616640
|Study Director:||Lars Sternas, MD, PhD||Celgene Corporation|
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Other Study ID Numbers:||
|First Posted:||November 30, 2015 Key Record Dates|
|Last Update Posted:||April 27, 2023|
|Last Verified:||April 2023|
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Blood Protein Disorders
Immune System Diseases
Peripheral Nervous System Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Immunological