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

Primary Purpose

Asymptomatic COVID-19 Infection Laboratory-Confirmed, B-Cell Neoplasm, Chronic Lymphocytic Leukemia

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ibrutinib

Quality-of-Life Assessment

About this trial

This is an interventional treatment trial for Asymptomatic COVID-19 Infection Laboratory-Confirmed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Cohort I (ibrutinib)

Cohort II Arm 2A (ibrutinib)

Cohort II Arm 2B (temporary interruption)

Arm Description

Patients may continue to receive ibrutinib PO daily or stop ibrutinib per provider's discretion.

Patients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity.

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.

Outcomes

Primary Outcome Measures

Proportion of patients who require hospitalization for their COVID-19 disease or die (Cohort 1)

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.

Proportion of patients who require mechanical ventilation and/or die (Cohort 2)

Secondary Outcome Measures

Rate of "flare phenomena" (Cohort I)

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.

Patient-reported health and symptom status (Cohort I)

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.

Patterns on ibrutinib therapy during COVID-19 infection (Cohort I)

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.

Reasons for hospitalization (Cohort I)

Mortality (Cohort II)

Time to hospital discharge (Cohort II)

Intubation and oxygen supplementation (Cohort II)

Will characterize and summarize the need for and duration of oxygen supplementation.

Incidence of "flare phenomena" (Cohort II)

Viral clearance

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.

Development of COVID-19 antibodies

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.

Coagulopathy and thrombosis measures

Cytokine measures

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.

Immune subset measures

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.

Full Information

NCT ID

NCT04665115

First Posted

December 10, 2020

Last Updated

August 2, 2022

Sponsor

Academic and Community Cancer Research United

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT04665115

Brief Title

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

Official Title

A Prospective Study of Patients With B-Cell Hematologic Malignancies on Ibrutinib Therapy Who Are Infected With Coronavirus Disease 2019 (COVID-19)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Permanently closed 11/19/201. The widespread availability of COVID vaccination, the projected decline in infection rates, and the increasing use of non-ibrutinib containing BTKi therapy, we have not been able to get support for this study

Study Start Date

November 23, 2020 (Actual)

Primary Completion Date

November 19, 2021 (Actual)

Study Completion Date

July 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Academic and Community Cancer Research United

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

Detailed Description

PRIMARY OBJECTIVES: I. To characterize and describe the patterns of temporary interruption vs. continuation of ibrutinib after their coronavirus disease 2019 (COVID-19) diagnosis and their corresponding rates of hospitalization and/or death by day 28 in an observational cohort of COVID-19 infected patients treated with ibrutinib therapy as their standard of care. (Cohort 1) II. To determine if continuation of ibrutinib during COVID-19 infection among patients who are hospitalized can result in decreased need for mechanical ventilation and decreased mortality by day 28 compared to patients who suspend temporarily ibrutinib treatment after their COVID-19 diagnosis. (Cohort 2) SECONDARY OBJECTIVES I. To determine the average length of time from diagnosis of COVID-19 infection to need for hospitalization due to worsening disease. (Cohort 1) II. To determine the rate of viral clearance on days 15, 28, 42, and 56 after registration. (Cohort 1) III. To evaluate coagulation parameters at baseline, and on days 15 and 28 after registration. (Cohort 1) IV. To determine the incidence of arterial and venous thrombosis as well as bleeding complications. (Cohort 1) V. To evaluate patient-reported health status and quality of life using the patient reported outcome (PRO)-Common Terminology Criteria for Adverse Events (CTCAE). (Cohort 1) VI. To determine if patients develop a "flare phenomenon" if ibrutinib is stopped. (Cohort 1) VII. To evaluate the patterns and timing of restarting ibrutinib in those patients who suspended their ibrutinib treatment after their COVID-19 diagnosis. (Cohort 1) VIII. To evaluate the association of patient outcomes stratified by the Charlson Co-morbidity index (CCI). (Cohort 1) IX. To evaluate the safety and tolerability of continuation of ibrutinib. (Cohort 1) X. To evaluate if continued treatment with ibrutinib can reduce the proportion of patients who die due to any cause in the 28 days after randomization compared to patients who stop ibrutinib in COVID-19 positive patients who are hospitalized at the time of study enrollment. (Cohort 2) XI. To evaluate the incidence of mechanical ventilation in hospitalized patients, and whether continued ibrutinib therapy reduces this incidence compared to stopping ibrutinib. (Cohort 2) XII. To determine whether continued ibrutinib can significantly improve the viral clearance rate at baseline, and on days 8, 15, 28, 42 and 56 days after randomization compared to those who temporarily interrupt ibrutinib. (Cohort 2) XIII. To evaluate coagulation parameters at baseline, and on days 8, 15, and 28 after randomization among patients who continue ibrutinib compared to those who discontinue ibrutinib. (Cohort 2) XIV. To determine the incidence of arterial and venous thrombosis as well as bleeding complications in patients who continue ibrutinib compared to those who stop it. (Cohort 2) XV. To determine if patients who are randomized to stopping ibrutinib develop "flare phenomenon". (Cohort 2) XVI. To evaluate the association of patient outcomes stratified by the Charlson Co-morbidity index (CCI). (Cohort 2) CORRELATIVE RESEARCH OBJECTIVES: I. To evaluate the association of inflammatory status with COVID severity. II. To determine the proportion of patients who develop antibodies to SARS-CoV2, especially given that patients with B cell malignancies tend to have inadequate responses to vaccines and often suffer from hypogammaglobulinemia. III. To determine changes in the immune profile by advanced flow cytometry given that the status of the immune system , both innate and adaptive , may dictate ultimate host management and clearance of COVID infections. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I: Patients may continue to receive ibrutinib orally (PO) daily or stop ibrutinib per provider's discretion. COHORT II: Patients are randomized to 1 of 2 arms. ARM 2A: Patients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity. ARM 2B: 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. After completion of study treatment, patients are followed up at 42, 56, and 84 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort I (ibrutinib)

Arm Type

Experimental

Arm Description

Patients may continue to receive ibrutinib PO daily or stop ibrutinib per provider's discretion.

Arm Title

Cohort II Arm 2A (ibrutinib)

Arm Type

Experimental

Arm Description

Patients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity.

Arm Title

Cohort II Arm 2B (temporary interruption)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ibrutinib

Other Intervention Name(s)

BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Quality-of-Life Assessment

Other Intervention Name(s)

Quality of Life Assessment

Intervention Description

Ancillary studies

Primary Outcome Measure Information:

Title

Proportion of patients who require hospitalization for their COVID-19 disease or die (Cohort 1)

Description

Time Frame

Up to 28 days after study registration

Title

Proportion of patients who require mechanical ventilation and/or die (Cohort 2)

Time Frame

Up to 28 days after study entry

Secondary Outcome Measure Information:

Title

Rate of "flare phenomena" (Cohort I)

Description

Time Frame

Up to 84 days

Title

Patient-reported health and symptom status (Cohort I)

Description

Time Frame

Up to 84 days

Title

Patterns on ibrutinib therapy during COVID-19 infection (Cohort I)

Description

Time Frame

Up to 84 days

Title

Reasons for hospitalization (Cohort I)

Time Frame

Up to 84 days

Title

Mortality (Cohort II)

Time Frame

Up to 84 days

Title

Time to hospital discharge (Cohort II)

Time Frame

Up to 84 days

Title

Intubation and oxygen supplementation (Cohort II)

Description

Will characterize and summarize the need for and duration of oxygen supplementation.

Time Frame

Up to 84 days

Title

Incidence of "flare phenomena" (Cohort II)

Time Frame

Up to 84 days

Title

Viral clearance

Description

Time Frame

On days 15, 28, 42, and 56 after registration

Title

Development of COVID-19 antibodies

Description

Time Frame

Up to 28 days

Title

Coagulopathy and thrombosis measures

Time Frame

Up to 28 days

Title

Cytokine measures

Description

Time Frame

Up to 84 days

Title

Immune subset measures

Description

Time Frame

Up to 84 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sameer A Parikh

Organizational Affiliation

Academic and Community Cancer Research United

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Rochester

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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