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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02684617




Registration number
NCT02684617
Ethics application status
Date submitted
12/02/2016
Date registered
18/02/2016

Titles & IDs
Public title
Study of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Hematologic Malignancies (MK-3475-155/KEYNOTE-155)
Scientific title
Phase Ib Trial of Pembrolizumab (MK-3475) in Combination With Dinaciclib (MK-7965) in Subjects With Hematologic Malignancies (KEYNOTE-155).
Secondary ID [1] 0 0
MK-3475-155
Secondary ID [2] 0 0
3475-155
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
rrCLL 0 0
rrMM 0 0
rrDLBCL 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - pembrolizumab
Treatment: Drugs - dinaciclib

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.

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.

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.


Treatment: Other: pembrolizumab
200 mg administered as an intravenous (IV) infusion on Day 1 of infusion Cycles 1-35. Each cycle is 21 days.

Treatment: Drugs: 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. Each cycle is 21 days.
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose Limiting Toxicity (DLT)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to 42 days
Primary outcome [2] 0 0
Number of Participants Who Experienced an Adverse Event
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 582 days
Primary outcome [3] 0 0
Number of Participants Who Discontinued Treatment Due to an Adverse Event
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Up to 492 days
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Up to approximately 26 months
Secondary outcome [2] 0 0
Duration of Response (DOR)
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 26 months
Secondary outcome [3] 0 0
Progression-Free Survival (PFS)
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Up to approximately 26 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Up to approximately 44 months

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/03/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/04/2020
Sample size
Target
Accrual to date
Final
75
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan
Statistical analysis plan Study Protocol and Statistical Analysis Plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02684617