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Trial record 1 of 1 for:    "Keynote-023"
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A Study of Pembrolizumab (MK-3475) in Combination With Standard of Care Treatments in Participants With Multiple Myeloma (MK-3475-023/KEYNOTE-023)

This study is currently recruiting participants.
Verified September 2017 by Merck Sharp & Dohme Corp.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02036502
First Posted: January 15, 2014
Last Update Posted: September 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose

This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory Multiple Myeloma (rrMM), and in combination with carfilzomib and low-dose dexamethasone in participants with relapsed or refractory Multiple Myeloma (rMM).

This study is being done to find the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D), and to evaluate the safety and tolerability of pembrolizumab when given in combination with standard of care (SOC) treatments in participants with rrMM or rMM. Preliminary efficacy data will also be assessed. The primary study hypothesis is that these combinations are sufficiently well tolerated to permit further clinical investigation.


Condition Intervention Phase
Multiple Myeloma Biological: Pembrolizumab Drug: Lenalidomide Drug: Dexamethasone Drug: Carfilzomib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination With Backbone Treatments for Subjects With Multiple Myeloma.

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (up to 28 days) ]
  • Number of Participants Experiencing AEs [ Time Frame: Up to 4 years ]
  • Number of Participants Discontinuing Study Drug Due to an AE [ Time Frame: Up to 4 years ]

Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Baseline and Day 1 of each 28-day cycle (up to 4 years) ]
  • Number of Participants with Complete Response (CR) [ Time Frame: Baseline and Day 1 of each 28-day cycle (up to 4 years) ]
  • Number of Participants with Stringent CR (sCR) [ Time Frame: Baseline and Day 1 of each 28-day cycle (up to 4 years) ]
  • Time to Progression (TTP) [ Time Frame: Up to 4 years ]
  • Duration of Response (DOR) [ Time Frame: Up to 4 years ]
  • Progression-Free Survival (PFS) [ Time Frame: Up to 4 years ]
  • Overall Survival (OS) [ Time Frame: Up to 4 years ]
  • Change from Baseline in Programmed Cell Death Ligand 1 (PD-L1) Expression in Responders Versus Non-Responders [ Time Frame: Baseline and Day 1 of each 28-day cycle (up to 4 years) ]
  • Disease Control Rate (DCR) [ Time Frame: Up to 4 years ]

Estimated Enrollment: 115
Actual Study Start Date: February 14, 2014
Estimated Study Completion Date: August 9, 2018
Estimated Primary Completion Date: August 9, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Determination Arm
Participants receive pembrolizumab 2 mg/kg every 2 weeks (Q2W, Days 1 and 15) in combination with lenalidomide 10 mg or 25 mg (Days 1-21) and dexamethasone 40 mg weekly during each 28-day cycle.
Biological: Pembrolizumab
Intravenous (IV) infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Lenalidomide
Oral capsule
Other Name: REVLIMID®
Drug: Dexamethasone
Oral tablet
Other Name: DECADRON®
Experimental: Dose Confirmation Arm
Participants receive pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg or 25 mg (Days 1-21) and dexamethasone 40 mg weekly during each 28-day cycle.
Biological: Pembrolizumab
Intravenous (IV) infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Lenalidomide
Oral capsule
Other Name: REVLIMID®
Drug: Dexamethasone
Oral tablet
Other Name: DECADRON®
Experimental: Cohort 1: rrMM
Participants receive pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg weekly during each 28-day cycle.
Biological: Pembrolizumab
Intravenous (IV) infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Lenalidomide
Oral capsule
Other Name: REVLIMID®
Drug: Dexamethasone
Oral tablet
Other Name: DECADRON®
Experimental: Cohort 2: rMM
Participants receive pembrolizumab 200 mg every 3 weeks (Q3W) in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
Biological: Pembrolizumab
Intravenous (IV) infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Dexamethasone
Oral tablet
Other Name: DECADRON®
Drug: Carfilzomib
IV infusion
Other Name: KYPROLIS®

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All Participants:

  • Confirmed diagnosis of multiple myeloma (MM)
  • Measurable disease
  • Archival or newly obtained bone marrow material available. In addition, for participants in the United States (US) and Canada, able to provide newly obtained bone marrow aspirate for biomarker analysis.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
  • Male participants must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study treatment through 120 days after the last dose of study treatment
  • Able to swallow capsules and able to take or tolerate oral medications on a continuous basis

Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

  • Failed at least 2 lines of prior therapy (e.g. bortezomib or carfilzomib and either thalidomide, pomalidomide, or lenalidomide)
  • Prior anti-MM treatments must have included an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
  • Must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; willing and able to comply with the regional requirements (for example, periodic pregnancy tests and safety labs)

Cohort 2 Participants:

  • MM with relapsing or refractory disease at study entry
  • Received prior treatment with 1 to 3 lines for MM
  • Achieved a partial response to at least one prior regimen (defined as ≥50% decrease in tumor burden)
  • Left ventricular ejection fraction of at least 40%

Exclusion Criteria:

All Participants:

  • Currently participating in and receiving study therapy or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment
  • History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or Waldenström's macroglobulinemia
  • Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy within 7 days prior to the first dose of study treatment
  • Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from a baseline AE or a Grade 1 AE associated with agents administered more than 4 weeks earlier
  • Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent
  • An additional malignancy that is progressing or requires active treatment within the last 5 years
  • Clinically active central nervous system (CNS) involvement
  • Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Active infection requiring intravenous systemic therapy
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment
  • Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agent
  • Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
  • Clinically significant coagulopathy
  • Known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Has had or is planning for allogeneic stem cell transplant
  • Autologous stem cell transplant within 12 weeks before the first infusion
  • History of Grade 4 rash associated with thalidomide treatment
  • Known hypersensitivity to thalidomide, lenalidomide or pomalidomide
  • Received a live vaccine within 30 days of planned start of study treatment

Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

  • Known gastrointestinal disease that may significantly alter the absorption of lenalidomide
  • Unable or unwilling to undergo antithrombotic prophylactic treatment

Cohort 2 Participants:

  • Smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia
  • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to the first dose of study treatment
  • Myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker.
  • Known history of allergy to CAPTISOL® (a cyclodextrin derivative used to solubilize carfilzomib)
  • Hypersensitivity to carfilzomib, bortezomib, boron, or mannitol
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first dose of study treatment
  • Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first dose of study treatment
  Contacts and Locations
Information from the National Library of Medicine

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): NCT02036502


Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
United States, California
Call for Information (Investigational Site 0018) Recruiting
La Jolla, California, United States, 92093
United States, Connecticut
Call for Information (Investigational Site 0019) Recruiting
New Haven, Connecticut, United States, 06520
United States, Massachusetts
Call for Information (Investigational Site 0001) Recruiting
Boston, Massachusetts, United States, 02215
Call for Information (Investigational Site 0002) Recruiting
Boston, Massachusetts, United States, 02215
United States, New Jersey
Call for Information (Investigational Site 0004) Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Call for Information (Investigational Site 0024) Recruiting
Lake Success, New York, United States, 11042
United States, Texas
Call for Information (Investigational Site 0003) Recruiting
Houston, Texas, United States, 77030
Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 4M7
Contact: Medical Information Centre Centre d'information medicale Merck Canada Inc.    514-428-8600 / 1-800-567-2594      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02036502     History of Changes
Other Study ID Numbers: 3475-023
2013-003512-44 ( EudraCT Number )
First Submitted: January 13, 2014
First Posted: January 15, 2014
Last Update Posted: September 25, 2017
Last Verified: September 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Lenalidomide
Pembrolizumab
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents