- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02684617
Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
February 9, 2021 updated by: Merck Sharp & Dohme LLC
Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
The purpose of this study is to evaluate 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).
Study Overview
Status
Terminated
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
75
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Relapsed or refractory chronic lymphocytic leukemia (rrCLL) 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
Relapsed or refractory multiple myelolma (rrMM) 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
Diffuse large B-cell lymphoma (rrDLBCL) 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 an active infection requiring intravenous systemic therapy
- 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
- 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
Relapsed or refractory chronic lymphocytic leukemia (rrCLL) participants:
- Has Richter's Transformation
Relapsed or refractory multiple myelolma (rrMM) participants:
- 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)
Diffuse large B-cell lymphoma (rrDLBCL) participants:
- Participants with primary mediastinal B-cell lymphoma (PMBCL)
- Has Richter's Transformation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: rrCLL Cohort
Participants with refractory chronic lymphocytic leukemia (rrCLL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8.
Each cycle is 21 days.
|
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35.
Each cycle is 21 days.
Other Names:
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.
Each cycle is 21 days.
Other Names:
|
Experimental: rrMM Cohort
Participants with relapsed or refractory multiple myeloma (rrMM) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8.
Each cycle is 21 days.
|
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35.
Each cycle is 21 days.
Other Names:
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.
Each cycle is 21 days.
Other Names:
|
Experimental: rrDLBCL Cohort
Participants with relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 7 mg/m^2 on Cycle 1 Day 1, and infusion of dinaciclib 10 mg/m^2 alone on Cycle 1 Day 8. Participants then received an infusion of pembrolizumab 200 mg followed by infusion of dinaciclib 14 mg/m^2 on Cycles 2-35 Day 1 and infusion of dinaciclib 14 mg/m^2 alone on Cycles 2-35 Day 8.
Each cycle is 21 days.
|
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35.
Each cycle is 21 days.
Other Names:
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.
Each cycle is 21 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame: Up to 42 days
|
DLTs consisted of the following if observed during treatment Cycles 1 or 2 and assessed by investigator to be possibly, probably, or definitely related to pembrolizumab or dinaciclib: grade 4 non-laboratory nonhematologic toxicity; grade 4 hematologic toxicity lasting >7 days (except thrombocytopenia); grade 4 thrombocytopenia of any duration; grade 3 thrombocytopenia if associated with bleeding; any grade 3 non-laboratory nonhematologic toxicity, except grade 3 nausea, vomiting, or diarrhea, which was not considered a DLT unless lasting more than 3 days despite optimal supportive care; Grade 3 or Grade 4 nonhematologic laboratory abnormality that required medical intervention, led to hospitalization, or persisted for >1 week; grade 3 or 4 febrile neutropenia; any drug-related AE that caused participant to discontinue treatment during Cycles 1 or 2; grade 5 toxicity; treatment-related toxicity that caused a >2-week delay in initiation of treatment Cycle 2 or 3.
Each cycle was 21 days.
|
Up to 42 days
|
Number of Participants Who Experienced an Adverse Event
Time Frame: Up to approximately 582 days
|
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
The number of participants who experienced an AE was presented.
|
Up to approximately 582 days
|
Number of Participants Who Discontinued Treatment Due to an Adverse Event
Time Frame: Up to 492 days
|
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
The number of participants who discontinued study drug due to an adverse event is presented.
|
Up to 492 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to approximately 26 months
|
ORR is defined in participants with CLL as the percentage of participants who have a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) as assessed by the investigator; in participants with DLBCL as the above definition but per the Revised Response Criteria for Malignant Lymphoma (2007) as assessed by the investigator; and in participants with MM as the percentage of participants who have a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006) as assessed by the investigator.
|
Up to approximately 26 months
|
Duration of Response (DOR)
Time Frame: Up to approximately 26 months
|
DOR is the time from initial response to Progressive Disease (PD) or death, whichever occurred first.
A response was: in participants with CLL, a confirmed Complete Response (CR) or Partial Response (PR) per the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008); in participants with DLBCL, as above but per the Revised Response Criteria for Malignant Lymphoma (2007); and in participants with MM, a confirmed Stringent Complete Response (sCR), CR, PR, or Very Good Partial Remission (VGPR) per the International Uniform Response Criteria for Multiple Myeloma (2006).
The above guidelines also define PD by disease.
Assessments were by investigator.
Data were censored at last disease assessment documenting absence of PD for participants who: had no PD and were still on the trial; received antitumor treatment other than that of the trial; or were removed from trial prior to PD. DOR was analyzed using the product-limit (Kaplan-Meier) method for censored data.
|
Up to approximately 26 months
|
Progression-Free Survival (PFS)
Time Frame: Up to approximately 26 months
|
PFS was defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
PD evaluations were done based on the cancer-specific criteria of: the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines (2008) in participants with CLL; the Revised Response Criteria for Malignant Lymphoma (2007) in participants with DLBCL; and the International Uniform Response Criteria for Multiple Myeloma (2006) in participants with MM.
Assessments were by investigator.
PFS data were censored for participants with no PD or death at their last disease assessment, or at their last disease assessment prior to starting new anticancer treatment for those who did so.
PFS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
|
Up to approximately 26 months
|
Overall Survival (OS)
Time Frame: Up to approximately 44 months
|
OS was defined as the time from first dose of study treatment to death due to any cause.
Data were censored at the date of a participant's last follow-up.
OS was analyzed using the product-limit (Kaplan-Meier) method for censored data.
|
Up to approximately 44 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 29, 2016
Primary Completion (Actual)
April 6, 2020
Study Completion (Actual)
April 6, 2020
Study Registration Dates
First Submitted
February 12, 2016
First Submitted That Met QC Criteria
February 12, 2016
First Posted (Estimate)
February 18, 2016
Study Record Updates
Last Update Posted (Actual)
March 1, 2021
Last Update Submitted That Met QC Criteria
February 9, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3475-155
- MK-3475-155 (Other Identifier: Merck Protocol Number)
- KEYNOTE-155 (Other Identifier: Merck)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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