- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02362035
ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies (KEYNOTE145)
A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Arizona
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Tucson, Arizona, United States, 85704
- Research Site
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California
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Los Angeles, California, United States, 90095
- Research Site
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Colorado
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Denver, Colorado, United States, 80218
- Research Site
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District of Columbia
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Washington, District of Columbia, United States, 20007
- Research Site
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Illinois
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Niles, Illinois, United States, 60714
- Research Site
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Massachusetts
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Boston, Massachusetts, United States, 2215
- Research Site
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Minnesota
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Rochester, Minnesota, United States, 55905-0001
- Research Site
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Nebraska
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Omaha, Nebraska, United States, 68198-7680
- Research Site
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Ohio
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Columbus, Ohio, United States, 43210
- Research Site
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South Carolina
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Greenville, South Carolina, United States, 29605
- Research Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- Research Site
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Texas
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Dallas, Texas, United States, 75246
- Research Site
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Houston, Texas, United States, 77030
- Research Site
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San Antonio, Texas, United States, 78217
- Research Site
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Tyler, Texas, United States, 75702
- Research Site
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Virginia
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Fairfax, Virginia, United States, 22031
- Research Site
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Roanoke, Virginia, United States, 24014
- Research Site
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Washington
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Vancouver, Washington, United States, 98684
- Research Site
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Yakima, Washington, United States, 98902
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Main Inclusion Criteria:
- Diagnosis of a hematologic malignancy as documented by medical records and with histology based on criteria established by the World Health Organization (WHO).
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
- Agreement to use contraception during the study and for 90 days after the last dose of ACP-196 or 120 days after the last dose of pembrolizumab, if sexually active and able to bear or beget children.
- Completion of all therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 4 weeks before the start of study therapy.
- ANC ≥ 0.5 x 10^9/L or platelet count ≥ 50 x 10^9/L unless due to disease involvement in the bone marrow.
Main Exclusion Criteria:
- A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of study drugs, or put the study outcomes at undue risk.
- Central nervous system (CNS) involvement by lymphoma/leukemia
- Any therapeutic antibody within 4 weeks of first dose of study drugs.
- Total bilirubin > 1.5 x ULN; and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN.
- Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Acalabrutinib plus Pembrolizumab
A nonrandomized study that will be conducted in 2 stages. In the first stage, (Safety), subjects will receive Acalabrutinib Dose A orally administered (PO) twice daily (BID) in combination with Pembrolizumab Dose B administered every 3 weeks (Q3W). The second stage was an expansion of Cohorts with the same dose regimen as the first stage. An additional expansion in subjects with Myelofibrosis was planned but not conducted. |
Orally Administered (PO)
Other Names:
Intravenous Administered (IV)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment Emergent Adverse Events (AEs)
Time Frame: 104 weeks
|
Treatment-emergent AEs were defined as those events that occurred on or after the first dose of study drug, through the treatment phase, and within 30 days following the last dose of study drug.
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104 weeks
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Number of Participants With Grade 3-4 Adverse Events
Time Frame: 104 weeks
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Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03
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104 weeks
|
Number of Participants With Grade 5 Adverse Events
Time Frame: 104 weeks
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Number of participants with CTCAE Grade 5 (fatal) adverse events
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104 weeks
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Number of Participants With Any Study-Drug Related AE
Time Frame: 104 weeks
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Study drug-related AEs were those assessed by investigator as related to study treatment.
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104 weeks
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Number of Participants With Grade 3-4 Study-Drug Related AE
Time Frame: 104 weeks
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The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.
Drug-related AEs were those assessed by investigator as related to study treatment.
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104 weeks
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Number of Participants With Grade 5 Study-Drug Related AE
Time Frame: 104 weeks
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Grade 5 (fatal) AEs assessed by investigator as related to study treatment.
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104 weeks
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Number of Participants With Any SAE
Time Frame: 104 weeks
|
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
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104 weeks
|
Number of Participants With Grade 3-4 Any SAE
Time Frame: 104 weeks
|
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.
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104 weeks
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Number of Participants With Grade 5 Any SAE
Time Frame: 104 weeks
|
Grade 5 events were fatal events.
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
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104 weeks
|
Number of Participants With Any Study Drug-Related SAE
Time Frame: 104 weeks
|
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
Drug-related AEs were those assessed by investigator as related to study treatment.
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104 weeks
|
Number of Participants With Any Grade 3-4 Study Drug-Related SAE
Time Frame: 104 weeks
|
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
The severity of the AEs was assessed by NCI CTCAE Version 4.03 or higher.
Drug-related AEs were those assessed by investigator as related to study treatment.
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104 weeks
|
Number of Participants With Any Grade 5 Study Drug-Related SAE
Time Frame: 104 weeks
|
Grade 5 AEs were fatal events.
Serious AEs were those that resulted in death, were life-threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, resulted in a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to the investigational product, or were considered a significant medical event by the investigator based on medical judgment.
Drug-related AEs were those assessed by investigator as related to study treatment.
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104 weeks
|
Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay
Time Frame: 104 weeks
|
AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.
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104 weeks
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Number of Participants With AE Leading to Study Drug Discontinuation
Time Frame: 104 weeks
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An adverse event that resulted in the permanent discontinuation of study treatment in the study.
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104 weeks
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Number of Participants With AE Leading to Study Drug Delay
Time Frame: 104 weeks
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An adverse event that caused a temporary withholding of study treatment.
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104 weeks
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Number of Participants With AE Leading to Study Drug Modification
Time Frame: 104 weeks
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An adverse event that resulted in a reduction in the dosage of study treatment for that participant.
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104 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate
Time Frame: 104 weeks
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The percentage of subjects who achieve a partial response or complete response
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104 weeks
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Duration of Response
Time Frame: 104 weeks
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The interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause
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104 weeks
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Progression-free Survival
Time Frame: 104 weeks
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The interval from the first dose date of acalabrutinib or pembrolizumab to the earlier of the first documentation of objective disease progression or death from any cause
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104 weeks
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Overall Survival
Time Frame: 104 weeks
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The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause
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104 weeks
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Time to Next Treatment
Time Frame: 104 weeks
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The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment
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104 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: AstraZeneca Clinical Study Information Center, 1-877-240-9479 - information.center@astrazeneca.com
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Neoplasms by Site
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Leukemia, Lymphoid
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Lymphoma, B-Cell
- Chronic Disease
- Neoplasms
- Lymphoma
- Hematologic Neoplasms
- Multiple Myeloma
- Leukemia
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Hairy Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Pembrolizumab
- Acalabrutinib
Other Study ID Numbers
- ACE-LY-005
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.
All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
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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