ACP-196 (Acalabrutinib) in Combination With Pembrolizumab, for Treatment of Hematologic Malignancies

Multiple Myeloma Clinical Trial

— KEYNOTE145  

Official title:

A Phase 1b/2 Proof-of-Concept Study of the Combination of ACP-196 (Acalabrutinib) and Pembrolizumab in Subjects With Hematologic Malignancies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02362035
• Other study ID #: ACE-LY-005
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: February 20, 2015
• Est. completion date: April 1, 2026

Study information

• Verified date: April 2024
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is evaluating the safety, pharmacodynamics (PD), and efficacy of acalabrutinib and pembrolizumab in hematologic malignancies.

Description:

This is a Phase 1b/2, open-label, nonrandomized study that will be conducted in 2 stages. In the first stage, Part 1 of the study will determine the safety and preliminary efficacy of acalabrutinib and pembrolizumab in a limited group of B-cell malignancies. In the second stage, Part 2 allows for possible expansion cohorts into a wider range of B-cell malignancies, and Part 3 will evaluate the combination in subjects with myelofibrosis (MF).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 161
• Est. completion date: April 1, 2026
• Est. primary completion date: July 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Burkitt Lymphoma
• CLL
• Follicular Lymphoma (FL)
• Hairy Cell Leukemia
• Hematologic Neoplasms
• Hodgkin Lymphoma
• Indolent Non Hodgkin Lymphoma
• Leukemia
• Leukemia, Hairy Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma (MCL)
• Marginal Zone Lymphomas
• Mediastinal Large B Cell Lymphoma
• Multiple Myeloma
• Neoplasms
• Richter's Syndrome
• Small Lymphocytic Lymphoma (SLL)
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• Acalabrutinib
Orally Administered (PO)
• Pembrolizumab
Intravenous Administered (IV)

Locations

Country	Name	City	State
United States	Research Site	Boston	Massachusetts
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Fairfax	Virginia
United States	Research Site	Greenville	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	Niles	Illinois
United States	Research Site	Omaha	Nebraska
United States	Research Site	Roanoke	Virginia
United States	Research Site	Rochester	Minnesota
United States	Research Site	San Antonio	Texas
United States	Research Site	Tucson	Arizona
United States	Research Site	Tyler	Texas
United States	Research Site	Vancouver	Washington
United States	Research Site	Washington	District of Columbia
United States	Research Site	Yakima	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Acerta Pharma BV	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Adverse Events (AEs)	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.	104 weeks
Primary	Number of Participants With Grade 3-4 Adverse Events	Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03	104 weeks
Primary	Number of Participants With Grade 5 Adverse Events	Number of participants with CTCAE Grade 5 (fatal) adverse events	104 weeks
Primary	Number of Participants With Any Study-Drug Related AE	Study drug-related AEs were those assessed by investigator as related to study treatment.	104 weeks
Primary	Number of Participants With Grade 3-4 Study-Drug Related AE	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.	104 weeks
Primary	Number of Participants With Grade 5 Study-Drug Related AE	Grade 5 (fatal) AEs assessed by investigator as related to study treatment.	104 weeks
Primary	Number of Participants With Any SAE	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.	104 weeks
Primary	Number of Participants With Grade 3-4 Any SAE	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.	104 weeks
Primary	Number of Participants With Grade 5 Any SAE	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.	104 weeks
Primary	Number of Participants With Any Study Drug-Related SAE	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.	104 weeks
Primary	Number of Participants With Any Grade 3-4 Study Drug-Related SAE	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.	104 weeks
Primary	Number of Participants With Any Grade 5 Study Drug-Related SAE	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.	104 weeks
Primary	Number of Participants With AE Leading to Study Drug Discontinuation, Modification or Delay	AEs that discontinuation of study treatment, or a reduction in dosage, or a delay (temporary withholding) in treatment.	104 weeks
Primary	Number of Participants With AE Leading to Study Drug Discontinuation	An adverse event that resulted in the permanent discontinuation of study treatment in the study.	104 weeks
Primary	Number of Participants With AE Leading to Study Drug Delay	An adverse event that caused a temporary withholding of study treatment.	104 weeks
Primary	Number of Participants With AE Leading to Study Drug Modification	An adverse event that resulted in a reduction in the dosage of study treatment for that participant.	104 weeks
Secondary	Overall Response Rate	The percentage of subjects who achieve a partial response or complete response	104 weeks
Secondary	Duration of Response	The interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause	104 weeks
Secondary	Progression-free Survival	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	104 weeks
Secondary	Overall Survival	The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause	104 weeks
Secondary	Time to Next Treatment	The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment	104 weeks

External Links

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