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

Status: Closed to Accrual

Description

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.

Eligibility 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

Locations & Contacts

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: Active
Contact: Allison Claire Rosenthal
Phone: 855-776-0015
Email: rosenthal.allison@mayo.edu
Tucson
Banner University Medical Center - Tucson
Status: Active
Contact: Crystal Lynn Placencia
Phone: 520-694-1231
Email: cplacencia@email.arizona.edu

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: Active
Contact: Donna Fernando
Phone: 323-409-4388
Email: Donna.fernando@med.usc.edu

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Contact: Shaji K. Kumar
Phone: 507-538-7623
Email: kumar.shaji@mayo.edu

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Merck and Company Inc

Trial IDs

Primary ID 3475-155
Secondary IDs NCI-2016-00730, MK-3475-155
Clinicaltrials.gov ID NCT02684617