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Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155)

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ClinicalTrials.gov Identifier: NCT02684617
Recruitment Status : Recruiting
First Posted : February 18, 2016
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:

This is a non-randomized, open-label study evaluating the safety and efficacy of pembrolizumab (MK-3475) used in combination with dinaciclib (MK-7965) in the treatment of relapsed or refractory chronic lymphocytic leukemia (rrCLL), multiple myeloma (rrMM), or diffuse large B-cell lymphoma (rrDLBCL) in up to 138 participants from multiple sites.

During an initial Dose Evaluation phase (first 2 cycles) to determine Dose Limiting Toxicities (DLTs), dose combinations of pembrolizumab 200 mg followed by dinaciclib 7 mg/m^2, pembrolizumab 200 mg followed by dinaciclib 10 mg/m^2, and pembrolizumab 200 mg followed by dinaciclib 14 mg/m^2 will be evaluated. Following safety review of the Dose Evaluation Phase, approximately 30 participants each will be enrolled in rrCLL, rrMM, or DLBCL cohorts during the Signal Detection phase. For each disease type objective response rate (ORR) will be determined by disease specific criteria.

The rrMM cohort was closed to enrollment on 07-AUG-2017 due to lack of efficacy.


Condition or disease Intervention/treatment Phase
rrCLL rrMM rrDLBCL Biological: pembrolizumab Drug: dinaciclib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
Actual Study Start Date : March 29, 2016
Estimated Primary Completion Date : February 6, 2020
Estimated Study Completion Date : February 6, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab and Dinaciclib
During the Dose Evaluation phase of the study, 12 participants will receive an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7mg/m^2 on Cycle 1 Day 1 and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants will then receive an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14mg/m^2 on Day 1 and infusion of dinaciclib 14mg/m^2 alone on Day 8 on Cycles 2 through 35. The study design will be revised based on the number of DLTs in Cycle 1 and Cycle 2. If ≤4 DLTs occur, 30 participants per disease type will be enrolled in the Signal Detection Phase. If >5 DLTs occur, a lower dose will be evaluated in up to 24 additional participants.
Biological: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35
Other Names:
  • MK-3475
  • SCH 9000475
  • KEYTRUDA®

Drug: dinaciclib
dinaciclib 7 mg/m^2 administered as an IV infusion on Day 1 of infusion Cycle 1, dinaciclib 10 mg/m^2 administered as an IV infusion on Day 8 of infusion Cycle 1, dinaciclib 14 mg/m^2 administered as an IV infusion on Days 1 and 8 of infusion Cycles 2-35
Other Name: MK-7965




Primary Outcome Measures :
  1. Number of participants with Dose Limiting Toxicity (DLT) [ Time Frame: Cycles 1 and 2 (up to 42 days) ]
  2. Number of participants with Adverse Events (AEs) [ Time Frame: From time of first dose until the end of follow-up (up to 26 months) ]
  3. Number of participants discontinuing study drug due to AEs [ Time Frame: From time of first dose until the end of follow-up (up to 26 months) ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) (disease specific) [ Time Frame: From time of screening until end of follow-up (up to 26 months) ]


Information from the National Library of Medicine

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

Inclusion Criteria:

  • Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours of study start)
  • Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Cardiac function suitable for protocol-required hydration as determined by the investigator and/or cardiologist
  • Must be able to provide biopsy specimens obtained ≤3 months for biomarker analysis. If bone marrow biopsy was performed 3 months before screening but subject had anti-cancer treatment after biopsy, the bone marrow biopsy and aspiration should be repeated

CLL Participants:

  • Must have a confirmed diagnosis of CLL defined by 2008 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria
  • Must have received one prior therapy for CLL
  • Must meet one or more of the consensus criteria for initiating treatment

MM Participants:

  • Must have a confirmed diagnosis of active MM
  • Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and failed last line of treatment (disease progression ≤60 days of completion of last therapy)
  • Must have failed prior anti-myeloma treatments that have included an immunomodulatory drug (IMiD) (pomalidomide, lenalidomide, or thalidomide) AND proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination

DLBCL Participants:

  • Must have a confirmed diagnosis of DLBCL and have progressed following ≥2 lines of previous therapy, after autologous stem cell transplant, or not a candidate for autologous stem cell transplant
  • Must have measurable disease (≥1 lesion that is >15 mm in the longest diameter or by >10 mm in the short axis)

Exclusion Criteria:

  • Has been treated with a cytochrome P450 3A4 (CYP3A4) strong inhibitor or inducer within 7 days of enrollment
  • Has been treated with anti-cancer therapy or thoracic radiation therapy within 14 days
  • Has known clinically active central nervous system (CNS) involvement
  • Has a known history of immunosuppression or is receiving systemic steroid therapy or any other form of systemic immunosuppressive therapy within 7 days
  • Has had prior anti-cancer monoclonal antibody within 4 weeks of Study Day 1 or who has not recovered from adverse events due to agents administered >4 weeks earlier
  • Has undergone prior allogeneic hematopoetic stem cell transplantation within the last 5 years
  • Has a known additional malignancy that is progressing or requires active treatment
  • Has active autoimmune disease that has required systemic treatment in past 2 years
  • Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death ligand (PD-L) 1, 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 co-stimulation or checkpoint pathways) or chimeric antigen receptor (CAR)-T cell therapy or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Has been previously treated with a cyclin-dependent kinase (CDK) inhibitor
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • Has a known history of or is positive for hepatitis B (hepatitis B surface antigen reactive) or hepatitis C (hepatitis C virus RNA [qualitative] is detected)
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Participants with non-secretory or oligo-secretory myeloma, plasma cell leukemia or Waldenström's macroglobulinemia
  • History of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Participants with primary mediastinal B-cell lymphoma (PMBCL)
  • Participants with CLL or DLBCL who have Richter's Transformation
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has known current symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

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): NCT02684617


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

Locations
United States, California
Call for Information (Investigational Site 0024) Recruiting
Duarte, California, United States, 91010
Call for Information (Investigational Site 0036) Recruiting
Los Angeles, California, United States, 90033
United States, Michigan
Call for Information (Investigational Site 0014) Recruiting
Detroit, Michigan, United States, 48201
Call for Information (Investigational Site 0028) Recruiting
Detroit, Michigan, United States, 48202
United States, Minnesota
Call for Information (Investigational Site 0006) Recruiting
Rochester, Minnesota, United States, 55905
United States, New Jersey
Call for Information (Investigational Site 0003) Recruiting
New Brunswick, New Jersey, United States, 08903
United States, New York
Call for Information (Investigational Site 0026) Recruiting
Buffalo, New York, United States, 14263
United States, Ohio
Call for Information (Investigational Site 0002) Recruiting
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Call for Information (Investigational Site 0023) Recruiting
Hershey, Pennsylvania, United States, 17033
United States, Texas
Call for Information (Investigational Site 0017) Recruiting
Dallas, Texas, United States, 75246
United States, Washington
Call for Information (Investigational Site 0011) Recruiting
Seattle, Washington, United States, 98116
United States, Wisconsin
Call for Information (Investigational Site 0018) Recruiting
Madison, Wisconsin, United States, 53792
Australia
Merck Sharp & Dohme Recruiting
North Ryde, Australia
Contact: Australian Medical Information Centre    61 2 8988 8428      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02684617     History of Changes
Other Study ID Numbers: 3475-155
MK-3475-155 ( Other Identifier: Merck Protocol Number )
First Posted: February 18, 2016    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Pembrolizumab
Antineoplastic Agents