Asymptomatic COVID-19 Infection Laboratory-ConfirmedPhase 2NCT04665115
Ibrutinib for the Treatment of Patients With B-Cell Malignancies Who Are Infected With Coronavirus Disease 2019 (COVID-19)
A Phase 2 study testing Ibrutinib and Quality-of-Life Assessment in people with Asymptomatic COVID-19 Infection Laboratory-Confirmed and B-Cell Neoplasm, run by Academic and Community Cancer Research United at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asymptomatic COVID-19 Infection Laboratory-Confirmed, B-Cell Neoplasm, Chronic Lymphocytic Leukemia
- What is being tested?
- Ibrutinib and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Nov 2020to 22 Jul 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: A Prospective Study of Patients With B-Cell Hematologic Malignancies on Ibrutinib Therapy Who Are Infected With Coronavirus Disease 2019 (COVID-19)
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Asymptomatic COVID-19 Infection Laboratory-Confirmed, B-Cell Neoplasm, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Being tested
- Ibrutinib, Quality-of-Life Assessment
- Medical subject headings
- Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (ibrutinib) | Experimental | Patients may continue to receive ibrutinib PO daily or stop ibrutinib per provider's discretion. Receives: Drug: Ibrutinib; Other: Quality-of-Life Assessment |
| Cohort II Arm 2A (ibrutinib) | Experimental | Patients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity. Receives: Drug: Ibrutinib; Other: Quality-of-Life Assessment |
| Cohort II Arm 2B (temporary interruption) | Experimental | 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. Receives: Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 days after study registration
Proportion of patients who require mechanical ventilation and/or die (Cohort 2)
Measured: Up to 28 days after study entry
Secondary outcomes (13)
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.
Measured: Up to 84 days
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.
Measured: Up to 84 days
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.
Measured: Up to 84 days
Reasons for hospitalization (Cohort I)
Measured: Up to 84 days
Mortality (Cohort II)
Measured: Up to 84 days
Time to hospital discharge (Cohort II)
Measured: Up to 84 days
Intubation and oxygen supplementation (Cohort II)
Will characterize and summarize the need for and duration of oxygen supplementation.
Measured: Up to 84 days
Incidence of "flare phenomena" (Cohort II)
Measured: Up to 84 days
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.
Measured: On days 15, 28, 42, and 56 after registration
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.
Measured: Up to 28 days
Coagulopathy and thrombosis measures
Measured: Up to 28 days
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.
Measured: Up to 84 days
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.
Measured: Up to 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2020
- Study start23 Nov 2020
- Primary completion19 Nov 2021
- Study completion22 Jul 2022
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asymptomatic COVID-19 Infection Laboratory-ConfirmedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Academic and Community Cancer Research United
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sameer A Parikh, Principal investigator, Academic and Community Cancer Research United
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04665115
- Sponsor's protocol ID
- ACCRU-LY-2001
- Other IDs
- NCI-2020-11785, ACCRU-LY-2001, P30CA015083
- Status last verified
- Aug 2022
- First submitted
- 10 Dec 2020
- Last updated
- 3 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Patients With B-Cell Hematologic Malignancies on Ibrutinib Therapy Who Are Infected With Coronavirus Disease 2019 (COVID-19)
- ClinicalTrials.gov ID
- NCT04665115
- Acronym / sponsor ID
- ACCRU-LY-2001
- Conditions
- Asymptomatic COVID-19 Infection Laboratory-Confirmed, B-Cell Neoplasm, Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason 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
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Academic and Community Cancer Research UnitedUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 23 Nov 2020 (actual)
- Primary completion
- 19 Nov 2021 (actual)
- Study completion
- 22 Jul 2022 (actual)
- First posted
- 11 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort I (ibrutinib) | Experimental | Drug: Ibrutinib, Other: Quality-of-Life AssessmentPatients may continue to receive ibrutinib PO daily or stop ibrutinib per provider's discretion. |
| Cohort II Arm 2A (ibrutinib) | Experimental | Drug: Ibrutinib, Other: Quality-of-Life AssessmentPatients continue to receive ibrutinib PO daily in the absence of disease progression or unacceptable toxicity. |
| Cohort II Arm 2B (temporary interruption) | Experimental | Other: Quality-of-Life AssessmentPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 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:
- 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
Key exclusion criteria (33 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Given PO | Drug | Cohort I (ibrutinib), Cohort II Arm 2A (ibrutinib) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Cohort I (ibrutinib), Cohort II Arm 2A (ibrutinib), Cohort II Arm 2B (temporary interruption) |
Primary outcome
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.
Proportion of patients who require mechanical ventilation and/or die (Cohort 2)
Time frame: Up to 28 days after study entry
13 secondary outcomes
Rate of "flare phenomena" (Cohort I)
Time frame: Up to 84 days
Patient-reported health and symptom status (Cohort I)
Time frame: Up to 84 days
Patterns on ibrutinib therapy during COVID-19 infection (Cohort I)
Time frame: Up to 84 days
Reasons for hospitalization (Cohort I)
Time frame: Up to 84 days
Mortality (Cohort II)
Time frame: Up to 84 days
Time to hospital discharge (Cohort II)
Time frame: Up to 84 days
Intubation and oxygen supplementation (Cohort II)
Time frame: Up to 84 days
Incidence of "flare phenomena" (Cohort II)
Time frame: Up to 84 days
Viral clearance
Time frame: On days 15, 28, 42, and 56 after registration
Development of COVID-19 antibodies
Time frame: Up to 28 days
Coagulopathy and thrombosis measures
Time frame: Up to 28 days
Cytokine measures
Time frame: Up to 84 days
Immune subset measures
Time frame: Up to 84 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sameer A Parikh principal investigator
Academic and Community Cancer Research United
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib and Quality-of-Life Assessment in people with Asymptomatic COVID-19 Infection Laboratory-Confirmed and B-Cell Neoplasm, run by Academic and Community Cancer Research United at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who require hospitalization for their COVID-19 disease or die (Cohort 1) (time frame: Up to 28 days after study registration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2022.