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

Chronic Lymphocytic Leukemia Clinical Trial

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

Status Withdrawn

Clinical 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. 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Asymptomatic COVID-19 Infection Laboratory-Confirmed
• B-Cell Neoplasm
• Chronic Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Communicable Diseases
• COVID-19
• Infections
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Marginal Zone Lymphoma
• Small Lymphocytic Lymphoma
• Symptomatic COVID-19 Infection Laboratory-Confirmed
• Waldenstrom Macroglobulinemia

• NCT number: NCT04665115
• Study type: Interventional
• Source: Academic and Community Cancer Research United
• Status: Withdrawn
• Phase: Phase 2
• Start date: November 23, 2020
• Completion date: July 22, 2022