This study will collect information on immune response and adverse events aftervaccination against coronavirus disease (COVID-19) in a vulnerable patient cohort.Understanding the ability or disability to mount a protective immune response aftervaccination will help to counsel patients during the pandemic and support decisions onwhom to vaccinate and to identify patients who require other measures to protect themfrom COVID-19.
Rationale:
Patients with cancer have an increased risk of adverse outcome of COVID-19, which is
determined by their underlying disease and/or cancer treatment. Therefore, vaccination of
cancer patients against COVID-19 is recommended. However, phase III studies do not
provide robust information on efficacy and safety in this vulnerable population. In
patients with cancer, the disease itself, but also immunotherapy and chemotherapy, may
have a significant impact on the ability to develop an effective immune response to
COVID-19 vaccination, and could even increase the risk of adverse events.
Objective:
To assess immune response and adverse events after administration of one approved vaccine
against COVID-19 in patients with cancer treated with immunotherapy and/or chemotherapy.
Study design:
This is a prospective multicenter, multicohort study.
Study population:
Four cohorts will receive vaccination against COVID-19:
A. Individuals without cancer (N=246, i.e., partners of patients in cohort B, C, and D)
B. Patients with cancer treated with immunotherapy (N=135) C. Patients with cancer
treated with chemotherapy (N=246) D. Patients with cancer treated with
chemo-immunotherapy (N=246)
Intervention:
Participants will be vaccinated against COVID-19 with an approved vaccine. Blood will be
drawn at different time points by venipuncture and mucosal lining fluid will be collected
at 2 time points.
Main study parameters/endpoints:
The primary endpoint is the antibody based immune response on day 28 after the second
vaccination. Participants will be classified as responders or non-responders. The
definition of response is seroconversion defined as presence of SARS-CoV-2 spike
S1-specific IgG antibodies in individuals without measurable anti-S antibodies at
baseline. Participants who are seropositive at baseline will not be included in the
analysis of the primary endpoint. The percentage of responders of each patient cohort
will be compared with the percentage responders in the control group. Safety is a
secondary endpoint which will be reported in terms of percentage of solicited local and
systemic adverse events (AEs) graded according to severity. Other secondary endpoints
include longevity at 6 months and levels of severe acute respiratory syndrome coronavirus
2 (SARS-CoV-2) specific T cell responses.
Nature and extent of the burden and risks associated with participation, benefit and
group relatedness:
Participants will have to visit the hospital at 6 time points and participants who
receive a third vaccination will have 2 additional hospital visits. The vaccine will be
administered two times according to standard of care, with the option of a third
vaccination for participants without an adequate response after 2 vaccinations. Blood
will be drawn (~373 ml in total for participants receiving 2 vaccinations, and ~539ml in
participants receiving 3 vaccinations) prior to the vaccinations and at day 28 and 6
months, 11 months and 18 months after the second vaccination. Nasal mucosal lining fluid
samples will be collected at baseline and day 28 after the second vaccination in a
subgroup of patients. Blood sampling will give minor discomfort. Vaccination can cause
AEs including fatigue, chills, headache, myalgia, and pain at the injection site. For
seven days after each vaccination, participants will be asked to record local and
systemic reactions using a questionnaire. At baseline and at 3, 6, 9, 12, 15 and 18
months after the second vaccination, patients will be asked to complete questionnaires
about potential subsequent testing for SARS-CoV-2, diagnosis of COVID-19, and severity of
COVID-19.
This study will collect information on immune response and adverse events after
vaccination against COVID-19 in a vulnerable patient cohort. It will also explore immune
response and safety of a third vaccination in participants without an adequate antibody
response after the second vaccination. Understanding the ability or disability to mount a
protective immune response after vaccination will help to counsel patients during the
pandemic and support decisions on whom to vaccinate and to identify patients who require
other measures to protect them from COVID-19. Participants will be informed about their
antibody titer in a letter that includes an explanation about what this means to them.
This will be done after antibody measurements have been completed for day 28 after second
vaccination, and again after completion of measurements for 6 months and 28 days after
third vaccination, and 11 months and 18 months after the second vaccination.
Biological: mRNA-1273 SARS-CoV-2 vaccine from Moderna
All participants will receive two vaccinations against COVID-19 according to standard of
care.
Inclusion Criteria:
To be eligible to participate in this study, a subject must meet all of the following
criteria:
- Age of 18 years or older
- Life expectancy > 12 months
- Ability to provide informed consent
Additional criteria for cohort A:
• Partner of a participating patient
Additional criteria for cohort B:
- Histological diagnosis of a solid malignancy
- Treatment with monotherapy immune checkpoint inhibitor (ICI) against Programmed
Death 1 (PD1) or its ligand PD-L1 (in curative or non-curative setting)
- Last ICI administration within 3 months of vaccination
Additional criteria for cohort C:
- Histological diagnosis of a solid malignancy
- Treatment with cytotoxic chemotherapy (monotherapy and combination chemotherapy is
allowed, as well as a combination with radiotherapy, in curative or non-curative
setting)
- Last chemotherapy administration within 4 weeks of vaccination
Additional criteria for cohort D:
- Histological diagnosis of a solid malignancy
- Treatment with a PD1 or PD-L1 antibody in combination with cytotoxic chemotherapy
(in curative or non-curative setting)
- Last chemotherapy administration within 4 weeks of vaccination
- Last ICI administration within 3 months of vaccination
Exclusion criteria:
- Confirmed SARS-CoV-2 infection (current or previous)
- Women who are pregnant or breastfeeding
- Active hematologic malignancy
- Any immune deficiency not related to cancer or cancer treatment (e.g. inherited
immune deficiency or known infection with Human Immunodeficiency Virus)
- Systemic treatment with corticosteroids (> 10 mg daily prednisone equivalent) or
other immunosuppressive medication within 14 days of vaccination. Inhaled or topical
steroids, and adrenal replacement steroids (> 10 mg daily prednisone equivalent) are
permitted. In addition, standard of care with short course steroids to prevent
nausea and allergic reactions from chemotherapy or iodinated CT contrast is allowed.
Additional criteria for cohort A:
- Current or previous diagnosis of a solid malignancy, unless treated with curative
intent >5 years before enrolment and without signs of recurrence during proper
follow-up
- Previous history of a hematologic malignancy
Additional criteria for cohort B:
• Treatment with cytotoxic chemotherapy within 4 weeks of vaccination
Additional criteria for cohort C:
• Treatment with an ICI within 3 months of vaccination
NKI-AvL
Amsterdam, Netherlands
UMCG
Groningen, Netherlands
Erasmus MC
Rotterdam, Netherlands
E G de Vries, MD, PhD, Principal Investigator
UMCG