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Completed

NCT Number: NCT02362035

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

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

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Key information

Conditions

Follicular Lymphoma (FL) Blood Protein Disorders Burkitt Lymphoma CLL Cardiovascular Diseases Chronic Disease DNA Virus Infections Disease Attributes Epstein-Barr Virus Infections Hairy Cell Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Herpesviridae Infections Hodgkin Disease Hodgkin Lymphoma Immune System Diseases Immunoproliferative Disorders Indolent Non Hodgkin Lymphoma Infections Leukemia Leukemia, B-Cell Leukemia, Hairy Cell Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Follicular Lymphoma, Mantle-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Mantle Cell Lymphoma (MCL) Marginal Zone Lymphomas Mediastinal Large B Cell Lymphoma Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Richter's Syndrome Small Lymphocytic Lymphoma (SLL) Tumor Virus Infections Vascular Diseases Virus Diseases Waldenstrom Macroglobulinemia Waldenström Macroglobulinemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Research Site, Tucson, Arizona, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Acalabrutinib

Drug

Orally Administered (PO)

Other names: ACP-196

Pembrolizumab

Drug

Intravenous Administered (IV)

Other names: KEYTRUDA

Primary outcomes

  1. 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.

  2. Number of Participants With Grade 3-4 Adverse Events

    Time frame: 104 weeks

    Severity of AEs was graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.03

  3. Number of Participants With Grade 5 Adverse Events

    Time frame: 104 weeks

    Number of participants with CTCAE Grade 5 (fatal) adverse events

  4. Number of Participants With Any Study-Drug Related AE

    Time frame: 104 weeks

    Study drug-related AEs were those assessed by investigator as related to study treatment.

  5. Number of Participants With Grade 3-4 Study-Drug Related AE

    Time frame: 104 weeks

    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.

  6. Number of Participants With Grade 5 Study-Drug Related AE

    Time frame: 104 weeks

    Grade 5 (fatal) AEs assessed by investigator as related to study treatment.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Number of Participants With AE Leading to Study Drug Discontinuation

    Time frame: 104 weeks

    An adverse event that resulted in the permanent discontinuation of study treatment in the study.

  15. Number of Participants With AE Leading to Study Drug Delay

    Time frame: 104 weeks

    An adverse event that caused a temporary withholding of study treatment.

  16. Number of Participants With AE Leading to Study Drug Modification

    Time frame: 104 weeks

    An adverse event that resulted in a reduction in the dosage of study treatment for that participant.

Secondary outcomes

  1. Overall Response Rate

    Time frame: 104 weeks

    The percentage of subjects who achieve a partial response or complete response

  2. Duration of Response

    Time frame: 104 weeks

    The interval from the first documentation of response to the earlier of the first documentation of definitive disease progression or death from any cause

  3. Progression-free Survival

    Time frame: 104 weeks

    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

  4. Overall Survival

    Time frame: 104 weeks

    The time from the first dose date of acalabrutinib or pembrolizumab until date of death due to any cause

  5. Time to Next Treatment

    Time frame: 104 weeks

    The time from the first dose date of acalabrutinib or pembrolizumab to the start of the next treatment other than the study treatment

Sponsors and collaborators

Lead sponsor

Acerta Pharma BV

Industry

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

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

Acronym: KEYNOTE145

Important dates

Study start
2015
Primary completion
2020
Study completion
2025
First posted
Feb 12, 2015
Registry last updated
May 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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