Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 3 for:    COVID-19 | Ibrutinib
Previous Study | Return to List | Next Study

Ibrutinib for the Treatment of Patients With B-Cell Malignancies Who Are Infected With Coronavirus Disease 2019 (COVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04665115
Recruitment Status : Not yet recruiting
First Posted : December 11, 2020
Last Update Posted : January 22, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

Brief Summary:
This phase II trial studies the effects of ibrutinib in treating patients with B-cell malignancies who are infected with COVID-19. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ibrutinib is a first in class Bruton tyrosine kinase inhibitor (BTKi), for the treatment of B-cell malignancies. This study is being done to determine if taking ibrutinib after contracting COVID-19 will make symptoms better or worse.

Condition or disease Intervention/treatment Phase
Asymptomatic COVID-19 Infection Laboratory-Confirmed B-Cell Neoplasm Chronic Lymphocytic Leukemia Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Small Lymphocytic Lymphoma Symptomatic COVID-19 Infection Laboratory-Confirmed Waldenstrom Macroglobulinemia Drug: Ibrutinib Other: Quality-of-Life Assessment Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Study of Patients With B-Cell Hematologic Malignancies on Ibrutinib Therapy Who Are Infected With Coronavirus Disease 2019 (COVID-19)
Estimated Study Start Date : June 30, 2021
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : May 1, 2025


Arm Intervention/treatment
Experimental: Cohort I (ibrutinib)
Patients may continue to receive ibrutinib PO daily or stop ibrutinib per provider's discretion.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Experimental: Cohort II Arm 2A (ibrutinib)
Patients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Experimental: Cohort II Arm 2B (temporary interruption)
Patients undergo temporary interruption of ibrutinib for up to 28 days unless they are discharged home and are thought to be medically fit by the primary caregiver to resume therapy according to their primary treating oncologist.
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment




Primary Outcome Measures :
  1. Proportion of patients who require hospitalization for their COVID-19 disease or die (Cohort 1) [ Time Frame: Up to 28 days after study registration ]
    Will calculate the proportion of patients who were outpatient at the time of study entry, and evaluate whether or not patients in this cohort required hospitalization associated with their coronavirus disease 2019 (COVID-19) infection.

  2. Proportion of patients who require mechanical ventilation and/or die (Cohort 2) [ Time Frame: Up to 28 days after study entry ]

Secondary Outcome Measures :
  1. Rate of "flare phenomena" (Cohort I) [ Time Frame: Up to 84 days ]
    Will characterize and calculate the proportion of patients who develop a "flare phenomenon" if ibrutinib is stopped. Will calculate corresponding 95% exact binomial confidence intervals for these outcomes. These will be graphically and quantitatively compared, where chi-square or Mantel-Haenszel-Cochran tests will be used to compare the numbers of patients who have the incident event of interest between treatment arms or other groups of interest.

  2. Patient-reported health and symptom status (Cohort I) [ Time Frame: Up to 84 days ]
    We will evaluate and characterize baseline status and changes in 8 primary COVID-19 related symptoms in these outpatient subjects: fever, loss of smell, cough, shortness of breath, fatigue, aching muscles, diarrhea, and decreased appetite. These will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Resolution of symptoms will be defined as no fever, no loss of smell, and severity or frequency of the remaining six symptoms rated as 0 (none/never) or 1 (mild/rarely) on the PRO-CTCAE.

  3. Patterns on ibrutinib therapy during COVID-19 infection (Cohort I) [ Time Frame: Up to 84 days ]
    We will characterize and summarize overall and by B-cell histologic diagnosis whether or not patients suspend their ibrutinib therapy while in an outpatient setting during the first 28 days on study, and patterns of resumption of ibrutinib. Specifically, we will evaluate this outcome by assessing the number of days patients received ibrutinib in the first 28 days after enrollment on this trial.

  4. Reasons for hospitalization (Cohort I) [ Time Frame: Up to 84 days ]
  5. Mortality (Cohort II) [ Time Frame: Up to 84 days ]
  6. Time to hospital discharge (Cohort II) [ Time Frame: Up to 84 days ]
  7. Intubation and oxygen supplementation (Cohort II) [ Time Frame: Up to 84 days ]
    Will characterize and summarize the need for and duration of oxygen supplementation.

  8. Incidence of "flare phenomena" (Cohort II) [ Time Frame: Up to 84 days ]
  9. Viral clearance [ Time Frame: On days 15, 28, 42, and 56 after registration ]
    The proportions of patients who are documented as having viral clearance at the various time points will be summarized at each time point within each treatment arm. These proportions will be evaluated within as well as across the cohorts. Within each cohort, we will compare these rates at each of the time points using chi-square or Mantel-Haenszel-Cochran tests to assess differences between treatment arms or groups. Further, logistic regression models will be used to assess incidence of viral clearance and how treatment arm and other demographic and clinical factors affect the ability of patients to achieve viral clearance.

  10. Development of COVID-19 antibodies [ Time Frame: Up to 28 days ]
    The proportion of patients who are able to develop COVID-19 antibodies by days 15 and 28, defined as the number of patients who have a threshold level of detectable COVID-19 antibodies divided by the total number of patients in the specific cohort/arm.

  11. Coagulopathy and thrombosis measures [ Time Frame: Up to 28 days ]
  12. Cytokine measures [ Time Frame: Up to 84 days ]
    Will evaluate the baseline as well as change in plasma cytokines between treatment arms: IL-1beta, IL-1Ralpha, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL- IL-9, IL-10, IFNgamma, IP10, TNFalpha in longitudinal samples.

  13. Immune subset measures [ Time Frame: Up to 84 days ]
    Will evaluate the baseline as well as change in several immune cell subsets, including CD3 T cells, CD4 T-helper cells (and their subsets), CD8 T-suppressor cells (and their subsets), NK cells, B cells, and monocytes.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • REGISTRATION INCLUSION
  • (COHORT 1): Age >= 18 years
  • COHORT 1: Laboratory confirmed diagnosis of COVID-19 through confirmation of SARS-Co-V2 via reverse transcriptase polymerase chain reaction (RT-PCR) or any Food and Drug Administration (FDA) approved method. The date of test result is required to be =< 7 days prior to registration (NOTE: please use the date the test was resulted and NOT the date when the test was collected)
  • COHORT 1: Patient is on ibrutinib for the following approved FDA indications, including:

    • Chronic lymphocytic leukemia/Small lymphocytic lymphoma
    • Mantle cell lymphoma
    • Waldenstrom macroglobulinemia
    • Marginal zone lymphoma
  • COHORT 1: Patients have been on standard dose ibrutinib therapy (420 mg daily for chronic lymphocytic leukemia [CLL]/small lymphocytic lymphoma [SLL] and Waldenstrom/Waldenstrom macroglobulinemia, and 560 mg daily for mantle cell lymphoma and marginal zone lymphoma) for at least 6 months prior to diagnosis of COVID-19 infection; and there is no evidence of disease progression of the primary malignancy for which ibrutinib is being used

    • NOTE: Patients are allowed to receive standard treatment as per local institutional guidelines for the treatment of COVID-19 at the same time the patient is enrolled on this trial
  • COHORT 1: Provide informed written consent =< 7 days prior to registration
  • COHORT 1: Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

    • Note: During the active monitoring phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up. All of these visits will be virtual (phone or video) ONLY
  • COHORT 1: Willing to provide blood specimens for correlative research purposes
  • RANDOMIZATION INCLUSION
  • COHORT 2: Age >= 18 years
  • COHORT 2: Laboratory confirmed diagnosis of COVID-19 through confirmation of SARS-Co-V2 via RT-PCR or any FDA approved method. The date of test result is required to be =< 7 days prior to registration (NOTE: please use the date the test was resulted and NOT the date when the test was collected)
  • COHORT 2: Patient is on ibrutinib for the following approved FDA indications, including:

    • Chronic lymphocytic leukemia/Small lymphocytic lymphoma
    • Mantle cell lymphoma
    • Waldenstrom macroglobulinemia
    • Marginal zone lymphoma
  • COHORT 2: Patients have been on standard dose ibrutinib therapy (420 mg daily for CLL/SLL and Waldenstrom macroglobulinemia, and 560 mg daily for mantle cell lymphoma and marginal zone lymphoma) for at least 6 months prior to diagnosis of COVID-19 infection; and there is no evidence of disease progression of the primary malignancy for which ibrutinib is being used

    • NOTE: Patients are allowed to receive standard treatment as per local institutional guidelines for the treatment of COVID-19 at the same time the patient is enrolled on this trial
  • COHORT 2: Provide informed written consent =< 7 days prior to registration
  • COHORT 2: Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

    • Note: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up. All of these visits will be virtual (phone or video) ONLY
  • COHORT 2: Willing to provide blood specimens for correlative research purposes
  • COHORT 2: Absolute neutrophil count (ANC) > 750 cells/mm^3 (0.75 x 10^9/L)
  • COHORT 2: Platelet count > 50,000 cells/mm^3 (50 x 10^9/L)
  • COHORT 2: Estimated creatinine clearance (CrCl) >= 30 mL/min (Cockcroft-Gault)
  • COHORT 2: Bilirubin =< 2.0 x upper limit of normal (ULN) (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
  • COHORT 2: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x ULN
  • COHORT 2: Prothrombin time (PT)/International normal ratio (INR) < 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder)

Exclusion Criteria:

  • REGISTRATION EXCLUSION
  • COHORT 1: Patient is receiving ibrutinib therapy for chronic graft-versus-host disease (cGVHD)
  • COHORT 1: Patient is currently receiving (or has in the past 6 months) another treatment in combination with ibrutinib, such as anti-CD20 monoclonal antibody, BCL-2 antagonists such as venetoclax, or other novel treatments or chemotherapeutic agents. For clarification regarding specific medications not listed here, please discuss with the principal investigator
  • COHORT 1: Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while on study
  • COHORT 1: Concomitant use of a strong CYP3A inhibitor
  • COHORT 1: Vaccinated with a live, attenuated vaccine within 4 weeks
  • COHORT 1: Patients with chronic liver disease and hepatic impairment meeting Child Pugh class C
  • COHORT 1: History of stroke or intracranial hemorrhage within 6 months before registration
  • COHORT 1: History of bleeding diathesis (e.g. hemophilia, von Willebrand/Waldenstrom disease)
  • COHORT 1: Clinically significant cardiovascular disease, such as uncontrolled arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
  • COHORT 1: Chemotherapy for other malignancies
  • COHORT 1: Concurrent systemic immunosuppressant therapy within 21 days of the first dose of study drug with the exception of that which is part of the standard of care for COVID-19
  • COHORT 1: Major surgery within 4 weeks of registration
  • COHORT 1: Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 1 month of last dose of study drug. Male subjects who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug
  • RANDOMIZATION EXCLUSION
  • COHORT 2: Patient is receiving ibrutinib on a clinical trial for their underlying B-cell malignancy
  • COHORT 2: Patient is receiving ibrutinib therapy for chronic graft-versus-host disease (cGVHD)
  • COHORT 2: Patient is currently receiving (or has in the past 6 months) another treatment in combination with ibrutinib, such as anti-CD20 monoclonal antibody, BCL-2 antagonists such as venetoclax, or other novel treatments or chemotherapeutic agents. For clarification regarding specific medications not listed here, please discuss with the principal investigator
  • COHORT 2: Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while on study
  • COHORT 2: Concomitant use of a strong CYP3A inhibitor
  • COHORT 2: Vaccinated with a live, attenuated vaccine within 4 weeks of registration
  • COHORT 2: Patients with chronic liver disease and hepatic impairment meeting Child Pugh class B and C
  • COHORT 2: History of stroke or intracranial hemorrhage within 6 months before registration
  • COHORT 2: History of bleeding diathesis (e.g. hemophilia, von Willebrand disease)
  • COHORT 2: Clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to registration
  • COHORT 2: Chemotherapy for other malignancies
  • COHORT 2: Concurrent systemic immunosuppressant therapy =< 21 days of the first dose of study drug with the exception of that which is part of the standard of care for COVID-19
  • COHORT 2: Major surgery within 4 weeks of registration
  • COHORT 2: Female subjects who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 1 month of last dose of study drug. Male subjects who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug
  • COHORT 2: Patients stopped ibrutinib >= 7 days prior to registration, for any reason
  • COHORT 2: Patient is an active participant on investigational therapy through an Institutional Review Board (IRB) approved clinical trial for COVID-19 (NOTE: Participation through compassionate use protocol or expanded access is permitted)
  • COHORT 2: At time of registration, the patient requires:

    • Endotracheal intubation and mechanical ventilation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04665115


Locations
Layout table for location information
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Contact: ACCRU Operations    507-538-7448    ACCRU@mayo.edu   
Principal Investigator: Sameer A. Parikh         
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Sameer A Parikh Academic and Community Cancer Research United
Layout table for additonal information
Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT04665115    
Other Study ID Numbers: ACCRU-LY-2001
NCI-2020-11785 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-LY-2001 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: December 11, 2020    Key Record Dates
Last Update Posted: January 22, 2021
Last Verified: December 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Laboratory Infection
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Occupational Diseases