Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization

Myelodysplastic Syndrome Clinical Trial

Official title: Randomized Double-Blind Phase 2 Trial of Ibrutinib Versus Standard Treatment for COVID-19 Illness Requiring Hospitalization With Safety Lead-In

Status Completed

Clinical Trial Summary

This phase Ib/II trial studies the side effects and best dose of ibrutinib and how well it works in treating patients with COVID-19 requiring hospitalization. Ibrutinib may help improve COVID-19 symptoms by lessening the inflammatory response in the lungs, while preserving overall immune function. This may reduce the need to be on a ventilator to help with breathing.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the feasibility and tolerability of administering ibrutinib in COVID-19 infected patients and determining the recommended phase 2 dose (RP2D). (Phase Ib) II. To determine whether ibrutinib administration (Arm A) in cancer patients can diminish the need for artificial ventilation (mechanical ventilation, bilevel positive airway pressure [BiPAP] or extracorporeal membrane oxygenation [ECMO]) or death due to COVID-19 as compared to untreated control population receiving standard therapy (antiviral, chloroquine, hydroxychloroquine, cytokine blocking peptides or small molecules) (Arm B). (Phase II)

SECONDARY OBJECTIVES:

I. To determine the time to defervescence (oral temperature < 100.5 degrees Fahrenheit [F] for a 48 hour time period) among patients treated with ibrutinib (Arm A) versus control population receiving standard (Arm B) therapy.

II. To determine time to clinical resolution of need for supplemental oxygen (i.e. maintenance of oxygen saturation of 93% or greater on room air with ambulation).

III. To determine rate of intensive care unit (ICU) admission and length of ICU admission for patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

IV. To determine rate of shock requiring vasopressor support for patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

V. To determine the rate of secondary infection (bacterial, fungal, viral) for patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

VI. To determine the time to hospital discharge for patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

VII. To determine time to hospital discharge and rate of death for patients who cross over to ibrutinib (Arm A) from standard therapy (Arm B).

VIII. To determine grade 3 or higher toxicity observed in patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

IX. To determine time to mechanical ventilation, the number of days of mechanical ventilation per patient and total observed in patients treated with ibrutinib (Arm A) versus control population receiving standard therapy (Arm B).

EXPLORATORY OBJECTIVES:

I. To examine the impact of baseline clinical features (e.g. type of cancer, active therapy), duration of symptoms prior to admission and laboratory features (e.g. T cell count) on outcome for patients treated on this therapeutic study.

II. To determine the proportion of patients with viral clearance at end of ibrutinib therapy, time of hospital discharge and follow up thereafter among patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.

III. To determine the time and proportion of patients who develop immunoglobulin (Ig)M and IgG levels toward SARS-coronavirus (CoV)-2 treated with ibrutinib (Arm A) versus control treatment (Arm B).

IV. To examine immune cell subsets for absolute number, activation, exhaustion markers, and presence of maturation arrest (natural killer [NK] cells) at baseline and over time among patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.

V. To examine T-cell repertoire over time among patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.

VI. To determine the influence of epigenetic age, clonal hematopoiesis, and monoclonal B cell lymphocytosis (MBL) on treatment outcome.

VII. To determine serial change in inflammatory markers as CRP, ferritin, D-dimer and cytokines including IL6, IL1B, and TNF-alpha serum levels over time among patients treated with ibrutinib (Arm A) versus control (Arm B) treatment.

OUTLINE: This is a phase Ib, dose-escalation study followed by a phase II study.

The first 12 patients will all receive ibrutinib. In the randomized part, patients are randomized to 1 of 2 arms.

ARM A: Patients receive ibrutinib orally (PO) once daily (QD) on days 1-7. Treatment repeats every 7 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients who remain hospitalized or are re-admitted after 2 cycles may receive an additional 2 cycles per physician's discretion.

ARM B: Patients receive usual care. Patients who meet the requirement of mechanical ventilation may cross-over to Arm A.

After completion of study treatment, patients are followed up for up to 12 months. ;

Related Conditions & MeSH terms

• Anemia, Aplastic
• Aplastic Anemia
• COVID-19
• Hematopoietic and Lymphoid Cell Neoplasm
• Lymphocytosis
• Malignant Solid Neoplasm
• Monoclonal B-Cell Lymphocytosis
• Monoclonal Gammopathy of Undetermined Significance
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Neoplasms
• Paraproteinemias
• Symptomatic COVID-19 Infection Laboratory-Confirmed

• NCT number: NCT04439006
• Study type: Interventional
• Source: Ohio State University Comprehensive Cancer Center
• Status: Completed
• Phase: Phase 1
• Start date: October 23, 2020
• Completion date: September 20, 2022