A Multi-Center, Open-Label, Single-Arm Phase II Trial of Antibody Combination EVUSHELD (Tixagevimab and Cilgavimab) to Provide Passive Immunity Against COVID-19 in Vaccine Non-responsive Chronic Lymphocytic Leukemia
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Chronic Lymphocytic Leukemia
- Sponsor
- Sunnybrook Health Sciences Centre
- Locations
- 1
- Primary Endpoint
- Passive Immunity
- Status
- Withdrawn
- Last Updated
- 2 years ago
Overview
Brief Summary
Chronic lymphocytic leukaemia (CLL) is a common lymphoid malignancy affecting older adults. CLL patients are immunocompromised by the disease itself and by several of its therapies. It has now been shown that many CLL patients do not mount an antibody response following COVID-19 vaccination and are therefore at risk of COVID-19 infection. Furthermore, patients with hematologic malignancies are known to be at increased risk of severe infection if they do acquire COVID-19 infection.
The purpose of this trial is to document evidence of passive immunity to COVID-19 infection after EVUSHELD administration with serologic and neutralization assays at multiple post administration time points in patients with no response to standard of care vaccination to COVID-19.
This trial will include a single dose of EVUSHELD to be administered, with a 1-year follow-up period, comprising of 8 health status visits.
Blood samples will be taken at screening, baseline and at multiple health status visits over the course of the year for various antibody testing and analysis. T cell reactivity to COVID-19 epitopes will be studied at baseline and again monthly for 3 months in any participants that become infected with COVID-19.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have a diagnosis of CLL according to international working group CLL criteria
- •Treatment-naïve, post treatment or on-treatment for CLL
- •Male or female ≥ 18 years of age on day of signing informed consent
- •Weight ≥ 40 kg at the screening
- •Have received at least 2 standard of care SARS-CoV-2 vaccines within the last 18 months prior to enrolment. These vaccines may include all vaccines given in Canada since the beginning of the pandemic including: Pfizer BNT162b2 (COMIRNATY®), Moderna mRNA-1273 (SPIKEVAX®), and Astra Zeneca AZD1222 (Vaxzevria®)
- •Last SARS-CoV-2 vaccination ≥28 days ago and no more than 18 months ago.
- •Participants must have a demonstrated absent or suboptimal response to standard of care SARS-CoV-2 vaccinations on screening bloodwork and will be prioritized for this study as they are deemed to be at higher risk of serious COVID-19 infection.
- •Have a performance status of 0-2 on the ECOG Performance Scale.
- •Have adequate organ function laboratory values, anytime during the screening period
- •Have a life expectancy \> 6 months in the opinion of the referring hematologist.
Exclusion Criteria
- •Signs and symptoms consistent with symptomatic COVID-19 illness within 30 days of consent.
- •Prior (within 30 days), current, or planned use of any of COVID-19 convalescent plasma, other monoclonal antibodies against SARS-CoV-2 or any COVID-19 treatment, or if clinically indicated as standard of care for a COVID-19 infection, should not be administered within 14 days of the EVUSHELD administration
- •Current infection requiring treatment with antibiotics or antifungals (not including prophylactic medications given with current therapy). Note: Participants completing a course of antibiotics for acute infection 7 days prior to SD0 and who do not experience a recurrence of symptoms or fever are eligible.
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Has known psychiatric or substance abuse disorders that would interfere with adherence with the requirements of the trial.
- •Previous hypersensitivity reaction following administration of a monoclonal antibody
- •Currently pregnant, lactating or breast feeding
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 21 days of treatment (SD0).
- •Receive a COVID-19 booster shot within 90 days of EVUSHELD administration
- •Known history of allergy to any component of the study drug formulation or its excipients
Outcomes
Primary Outcomes
Passive Immunity
Time Frame: 12 months
The primary study objective is to confer passive immunity to CLL patients, so the primary outcome measurement is the proportion of of participants after EVUSHELD administration with anti-spike antibodies above the minimal level set as a standard for convalescent serum or 210 u/ml using the Roche assay
Secondary Outcomes
- COVID-19 Infection (RAT/PCR)(12 months)
- Pseudo- Viral Naturalization Assay(12 months)
- Pharmacokinetic Assessments(12 months)
- Surrogate Viral Neutralization Assay(12 months)
- COVID-19 Infection (antibodies)(12 months)
- Symptomatic COVID-19 infection(12 months)
- Safety of EVUSHELD(12 months)
- Baseline T cell responses to COVID-19 as a potential predictor of breakthrough COVID-19 infections(12 months)