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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

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02616640
Collaborator
(none)
114
Enrollment
35
Locations
3
Arms
84.8
Anticipated Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
114 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 :
Jan 11, 2016
Actual Primary Completion Date :
Jan 10, 2017
Anticipated Study Completion Date :
Feb 3, 2023

Arms and Interventions

Arm Intervention/Treatment
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

Drug: Durvalumab
Other Names:
  • 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

    Drug: Durvalumab
    Other Names:
  • MEDI4736

    • Drug: Pomalidomide
    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

    Drug: Durvalumab
    Other Names:
  • MEDI4736

    • Drug: Pomalidomide

    Drug: Dexamethasone

    Outcome Measures

    Primary Outcome Measures

    1. Dose-limiting Toxicities (DLTs) [Approximately 1 month]

      Number of participants with DLTs in the first cycle of treatment

    Secondary Outcome Measures

    1. Adverse Events (AEs) [Up to approximately 2 year]

      Number of participants with adverse events

    2. Overall response rate (ORR) [Up to approximately 2 year]

      Tumor response, including progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria

    3. Time to response (TTR) [Up to approximately 2 year]

      Time from first dose to the first documentation of response (Partial Response [PR] or greater)

    4. Duration of response (DOR) [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

    5. Pharmacokinetics- Cmax [Up to approximately 1 year]

      Maximum observed concentration

    6. Pharmacokinetics- AUC [Up to approximately 1 year]

      Area under the concentration-time curve

    7. Pharmacokinetics- Tmax [Up to approximately 1 year]

      Time to maximum concentration

    8. Pharmacokinetics- t1/2 [Up to approximately 1 year]

      Terminal elimination half-life

    9. Pharmacokinetics- CL/F [Up to approximately 1 year]

      Apparent total body clearance

    10. Pharmacokinetics- Vz/F [Up to approximately 1 year]

      Volume of distribution

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Arkansas Little Rock Arkansas United States 72205
    2 Johns Hopkins Oncology Center Baltimore Maryland United States 21231
    3 Massachusetts General Hospital / Dana-Farber Cancer Institute Boston Massachusetts United States 02114
    4 Dana-Farber Partners Cancer Care, Inc. Boston Massachusetts United States 02115
    5 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    6 Hackensack University Medical Center Hackensack New Jersey United States 07601
    7 Mt. Sinai School of Medicine New York New York United States 10029
    8 Weill Medical College of Cornell University New York New York United States 10065
    9 Levine Cancer Institute Charlotte North Carolina United States 28204
    10 Cleveland Clinic Cleveland Ohio United States 44195
    11 Ohio State Medical Center Columbus Ohio United States 43210
    12 Froedtert Hospital BMT Medical College of Wisconsin Milwaukee Wisconsin United States 53226-3522
    13 Tom Baker Cancer Center Calgary Alberta Canada T2N 4N2
    14 CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang Lille France 59037
    15 CHU Nantes Hotel Dieu Nantes France 44093
    16 CHU Bordeaux Pessac France 33604
    17 CHU La Miletrie Poitiers Cedex France 86021
    18 Institut universitaire du cancer de Toulouse (IUCT) - Oncopole Toulouse CEDEX 9 France 31059
    19 Universitaetsklinikum Carl Gustav Carus Dresden Germany 01307
    20 Universitaetsklinikum EssenZentrum fuer Innere Medizin Essen Germany 45122
    21 University of Heidelberg Heidelberg Germany D-69120
    22 Universitaetsklinikum Jena Jena Germany 07740
    23 Universitaetsklinikum Tuebingen Tuebingen Germany 72076
    24 Istituto Nazionale Dei Tumori Milano Italy 20133
    25 Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" Napoli Italy 80131
    26 Policlinico San Matteo Universita Di Pavia Pavia 2 Italy 27100
    27 Istituto Clinico Humanitas Rozzano (MI) Italy 20089 Roz
    28 Azienda Ospedaliera Citta della Salute e della Scienza di Torino Torino Italy 10126
    29 VU University Medical Center VU Medisch Centrum Amsterdam Netherlands 1081 HV
    30 Erasmus Medical Center Rotterdam Netherlands 3015 CN
    31 ICO-Hospital Germans Trias i Pujol Barcelona Spain 08916
    32 Hospital 12 de Octubre Madrid Spain 28041
    33 Clinica Universidad de Navarra Pamplona Spain 31008
    34 Hospital Universitario de Salamanca Salamanca Spain 37007
    35 Hospital Universitari i Politecnic La Fe de Valencia Valencia Spain 46026

    Sponsors and Collaborators

    • Celgene

    Investigators

    • Study Director: Lars Sternas, MD, PhD, Celgene Corporation

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Celgene
    ClinicalTrials.gov Identifier:
    NCT02616640
    Other Study ID Numbers:
    • MEDI4736-MM-001
    First Posted:
    Nov 30, 2015
    Last Update Posted:
    Aug 5, 2021
    Last Verified:
    Aug 1, 2021
    Keywords provided by Celgene
    Multiple Myeloma
    Relapsed
    Refractory
    MEDI4736
    Durvalumab
    Pomalidomide (POM)
    Dexamethasone (DEX)
    PD-L1
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Durvalumab
    Pomalidomide

    Study Results

    No Results Posted as of Aug 5, 2021