Table 1.

Current Clinical Trials Investigating COVID-19 Vaccination in Patients with Cancer or Immunocompromised States.

Study Title & ClinicalTrials.gov Identifier	Country	Study Phase	Primary Outcome Measures	Study Participants & Inclusion Criteria	Intervention & Model	Results
Evaluation of the Effect and Side Effect Profile of COVID-19 Vaccine in Cancer Patients   Identifier: NCT04771559 [1,101]	Turkey	Complete	COVID-19 antibody titers. Time frame: 1 month	N = 1500 Patient group: Individuals aged 18+ diagnosed with cancer, who had received two doses of the COVID-19 vaccine Control group: Individuals aged 18+ with no history of cancer, who had received two doses of the COVID-19 vaccine	Intervention: COVID-19 antibody test.   Non-randomized, parallel assignment	Seropositivity rates at one month: Patient group: 85.2% Control group: 97.5% (p < 0.001)   Lower seropositivity in cancer patients associated with chemotherapy and age 60+ (p < 0.001)
Immune Response to the COVID-19 Vaccine   Identifier: NCT04936997 [101,102]	USA	Early Phase 1	Immune response to 2nd COVID-19 vaccination booster (3rd vaccine) in patients with solid malignancies on immunosuppressive therapy Time frame: 3 months	N = 20 Patient group: Individuals aged 18+ with active solid tumor malignancy on active chemotherapy, who had received two doses of the Pfizer COVID-19 vaccine	Intervention: SARS-COV2 Pfizer Vaccine   Single group assignment	80% (16/20) of participants demonstrated a median threefold increase in antibody response one week following a third dose of the Pfizer vaccine. No improvement was noted in T-cell responses. Adverse events were mild in nature.
Impact of the Immune System on Response to Anti-Coronavirus Disease 19 (COVID-19) Vaccine in Allogeneic Stem Cell Recipients (Covid Vaccin Allo)   Identifier: NCT04951323 [101]	Belgium	Phase 3	Quantification of anti-SARS-CoV-2 IgG antibodies after vaccination in allogenic stem cell recipients Time frame: 49 days following first injection	Estimated N = 50 Patient group: Individuals aged 18+ who had undergone allogeneic hematopoietic stem cell transplantation 3 months to 5 months prior. Patients were excluded if they had active malignant disease at the time of inclusion	Intervention: Anti-COVID19 mRNA-based vaccine (BNT162b2, Comirnaty®, commercialized by Pfizer) Single group assignment	N/A
Safety and Immunogenicity of COVID-19 Vaccination in Patients With Cancer   Identifier: NCT05018078 [101]	China	N/A	Primary Outcome 1: Safety of the COVID-19 vaccine, monitoring the occurrence of adverse effects Time frame: Within 2 months following the first vaccine dose   Primary Outcome 2: Immunogenicity of the COVID-19 vaccine, measuring antibody titers against SARS-CoV-2 Time frame: Within 2 months following the first vaccine dose	Estimated N = 300 Patient group: Individuals aged 18+, with a cancer diagnosis including hepatocellular carcinoma, breast cancer, lung cancer, esophageal cancer, gastric cancer or colorectal cancer. Individuals must have local or systemic anti-cancer therapies according to the treatment guidelines previously or currently, in stable condition with an Eastern Cooperative Oncology Group (ECOG) score below 2. Additionally, patients must have normal or basically normal multi-organ function, without contraindications to vaccination	Intervention: Coronavirus vaccine   Single group assignment	N/A
A Trial of the Safety and Immunogenicity of the COVID-19 Vaccine (mRNA-1273) in Participants With Hematologic Malignancies and Various Regimens of Immunosuppression, and in Participants With Solid Tumors on PD1/PDL1 Inhibitor Therapy, Including Booster Doses of Vaccine   Identifier: NCT04847050 [101]	USA	Phase 2	Primary Outcome 1: Safety and reactogenicity of the mRNA-1273 vaccine, soliciting local and systemic adverse reactions 7 days after each injection, and unsolicited adverse events up to 28 days post-injection Time frame: 14 months   Primary Outcome 2: Immunogenicity of the mRNA-1273 vaccine in patients with a hematological malignancy and are immunosuppressed due to their disease, and/or receiving PD-1/PDL-1 inhibitor for treatment of a solid tumor. Measured titers of specific binding antibody (bAb) on day 1, 29, 36, 57, 209, and 394 Time frame: 14 months	Estimated N = 220 Patient group: Individuals aged 18+ with either: -Solid tumor diagnosis, receiving PD1/PDL1 inhibitor treatment, -Diagnosis of acute leukemia (myeloid (AML) or lymphoid (ALL) or other); multiple myeloma; Waldenstrom macroglobulinemia, or -Diagnosis of lymphoma, including chronic lymphocytic leukemia Individuals must demonstrate adequate organ and bone marrow function on laboratory assessment within 4 weeks of vaccine administration	Intervention: mRNA-1273 injection.   Non-randomized, parallel assignment	N/A
The Immune Reaction Upon COVID-19 Vaccination in the Belgian Cancer Population.   Identifier: NCT05033158 [101]	Belgium	N/A	Immune response measuring quantification of anti-SARS-CoV-2 IgG antibodies (against full Spike, S1, S2, RBD, and N proteins) 4 weeks after first vaccine administration Time frame: 4 months	Estimated N = 3000 Patient group: Individuals aged 18+ with oncological or hematological malignancy, or a history of it, with a life expectancy >3 months	Intervention: Blood sampling   Single group assignment	N/A
SARS-CoV-2 Vaccine (COH04S1) Versus Emergency Use Authorization SARS-COV-2 Vaccine for the Treatment of COVID-19 in Patients With Blood Cancer   Identifier: NCT04977024 [101]	USA	Phase 2	Biological response, based on at least a 3-fold increase in anti-SARS-CoV-2 antibodies or interferon gamma levels Time frame: At 28 days post the second vaccine injection	Estimated N = 240 Patient group: Individuals aged 18+ with hematologic malignancy and an ECOG score of 2 or less. They must have received either allogenic or autologous hematopoietic cell transplant, or cellular therapy (chimeric antigen receptor [CAR] T-cell) therapy and be at least 3 months post treatment infusion	Interventions: COVID-19 Vaccine, Diagnostic Laboratory Biomarker Analysis, and Synthetic MVA-based SARS-CoV-2 Vaccine COH04S1   Randomized. parallel assignment	N/A
Safety and Immunogenicity of Prime-boost Vaccination of SARS-CoV-2 in Patients With Cancer   Identifier: NCT05273541 [101]	China	Phase 1 Phase 2	Primary Outcome 1: Determining the safety of the prime-boost vaccine, measuring the occurrence of adverse effects post-vaccination Time frame: Within 1 week after the prime-boost vaccination   Primary Outcome 2: Determining immunogenicity by titers of anti-SARS-CoV-2 antibodies Time frame: Within 3 months after the prime-boost vaccination	Estimated N = 100 Patient group: Individuals aged 18+, with a cancer diagnosis including hepatocellular carcinoma, breast cancer, lung cancer, esophageal cancer, gastric cancer or colorectal cancer. Individuals must have local or systemic anti-cancer therapies according to the treatment guidelines previously or currently, in stable condition with an ECOG score below 2. Additionally, patients must have normal or basically normal multi-organ function, without contraindications to vaccination.	Intervention: Coronavirus vaccination   Single group assignment	N/A
Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults   Identifier: NCT04952766 [101]	France	Phase 4	Protective humoral response post-vaccination, measuring the proportion of immunocompromised individuals with neutralizing activity against the “Wuhan” stain of SARS-CoV-2, as compared to healthy subjects Time frame: 2 months	N = 196 Adult volunteers belonging to one of the following groups: Immunocompromised group (~15 participants per subgroup): -Kidney transplant -Extracorporeal dialysis -Solid cancer, receiving chemotherapy and/or radiotherapy -Myeloma, receiving chemotherapy -Hematologic malignancy, receiving chemotherapy -Diseases treated with anti-CD20 (or, patients not treated at the time of vaccination, but will be immediately after) -Multiple sclerosis, receiving anti-CD20 (or, patients not treated at the time of vaccination, but will be immediately after) -Common variable immune deficiency, or other causes of severe hypogammaglobulinemia requiring chronic treatment with polyvalent immunoglobulin -Malignant tumor, receiving anti-PD1 or anti-PDL1 therapy -HIV -Complicated type 2 diabetes (with micro and/or macroangiopathy) Non-immunocompromised group: vaccinated with either Comirnaty TM or AstraZeneca’s Vaxzevria TM for the first dose	Intervention: Biological samples   Single group assignment	N/A
COVID-19 VAX Booster Dosing in Patients With Hematologic Malignancies   Identifier: NCT05028374 [101]	USA	Phase 2	Seroconversion rates of anti-SARS-CoV-2 antibody following a booster dose of the Moderna mRNA COVID-19 vaccine Time frame: 28 (±3 days) following booster dose	N = 119 Patient group: Individuals aged 18+ who have been previously diagnosed with multiple myeloma (MM)/amyloid light-chain amyloidosis, or other hematologic malignancy. They must have previously received any one of the available COVID-19 vaccines between 4–36 months prior to study enrollment, with anti-SARS-CoV-2 IgG titers less than 1.0 unit, or between 1.0–1.99 units. If patients are currently receiving potentially immunosuppressive cancer therapy, a two-week interruption before and after the booster dose of the vaccine is encouraged, but not required (at physician discretion)	Intervention: A single “booster” dose of the Moderna mRNA COVID-19 vaccine   Single group assignment	N/A
Booster Dose Trial   Identifier: NCT05016622 [101]	USA	Phase 2	Rates of seroconversion for SARS-CoV-2 anti-spike antibody Time frame: 4 weeks after booster dose	Estimated N = 100 Patient group: Individuals aged 18+ with a known diagnosis of any malignancy (either active or post completion of therapy), with negative SARS-CoV-2 spike IgG at least 14 days post-2nd dose of an mRNA-based COVID-19 vaccine, or 28 days after a single dose of the adenovirus-based Johnson & Johnson vaccine	Intervention: BNT162b2 vaccine   Single group assignment	N/A
Passive Antibodies Against COVID-19 With EVUSHELD in Vaccine Non-responsive CLL   Identifier: NCT05465876 [101]	Canada	Phase 2	Conferring passive immunity to CLL patients, measuring the proportion of participants with anti-spike antibodies after EVUSHELD administration Time frame: 12 months	Estimated N = 200 Patient group: Individuals aged 18+ with a diagnosis of CLL, who are either treatment-naïve, post-treatment, or on-treatment for CLL, and an ECOG score between 0–2. They must have received at least two doses of the Pfizer, Moderna, or AstraZeneca COVID-19 vaccines between 28 days-18 months prior to enrollment, demonstrating absent or suboptimal response. Participants must weigh at least 40 kg, have adequate organ function laboratory values, and have a life expectancy >6 months	Intervention: EVUSHELD   Single group assignment	N/A
Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial   Identifier: NCT05556720 [101]	Australia	Phase 3	Measuring the geometric mean concentration (GMC) of anti-spike SARS-CoV-2 IgG antibody Time frame: 28 days after completion of vaccination trials	Estimated N = 960 Patient group: Individuals aged 16+ who have completed 3–5 doses of an Australian Therapeutic Goods Administration approved COVID-19 vaccine (Pfizer, Moderna, AstaZeneca, or Novavax). Patients must be in one of the following populations: -HIV infection, -Current recipient of a solid organ transplant, including kidney, pancreas, liver, malignancy episodes of severe rejection, requiring T- or B-cell depletion in the past 3 months, or -Undergoing chemotherapy, immunotherapy, and/or targeted therapy, or completed said therapies within the past 2 years in treatment of CLL, MM, or non-Hodgkin lymphoma	Interventions: BNT162b2, mRNA-1273, or NVX-COV2373   Randomized, parallel assignment	N/A
Anti-COVID-19 Vaccine in Children With Acute Leukemia and Their Siblings   Identifier: NCT04969601 [101]	France	Phase 1 Phase 2	Primary Objective 1: Dose limiting toxicity, determined by the presence of grade ≥3 adverse events within 7 days following vaccine injection, that are deemed to be related to the vaccine Time frame: Within 7 days from first dose   Primary Objective 2: Four-times or higher increase in the anti-spike IgG titer, AND positive anti-spike neutralizing test, indicating significant seroconversion Time frame: At 2 months from first dose	Estimated N = 150 Patient group: Individuals aged 1–15 years, with either: -Acute lymphoblastic leukemia (ALL), undergoing chemotherapy (within 2 weeks from the last injection) or for whom the last chemotherapy treatment was less than/equal to 12 months, or -Acute myeloid leukemia (AML) within 12 months from the end of treatment Control group: Healthy siblings aged 1–15 years, living in the same household as the child with ALL/AML more than 50% of the time	Intervention: Vaccine COMIRNATY® (BNT162b2)   Single group assignment	N/A
Safety, Efficacy of BNT162b2 mRNA Vaccine in CLL   Identifier: NCT04862806 [101,103]	Israel	Complete	Primary Objective 1: Change in the number of participants with adverse events related to the BNT162b2 mRNA vaccine, assessed by a questionnaire with answers reported on a scale of 0–5 Time frame: 2–6 weeks after 2nd vaccination, 3 months after 2nd vaccination, 6 months after 2nd vaccination   Primary Objective 2: Antibody persistence following the 3rd dose of the BNT162b2 mRNA vaccine in seronegative patients with chronic lymphocytic leukemia Time frame: 6 months	Estimated N = 1000 Patient group: Individuals aged 18+ with a diagnosis of CLL, who have received two 30-μg doses of BNT162b2 3 weeks apart	Intervention: COVID-19 serology   Single group assignment	Of patients with CLL who failed to demonstrate a seropositive response following two doses of the BNT162b2 vaccine, nearly one fourth responded to a third dose of the vaccine. However, antibody responses were lower in patients undergoing active treatment, and patients with recent exposure (<12 months prior) to anti-CD20 therapy

Abbreviations: COVID-19, coronavirus disease 2019; USA, United States of America; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; IgG, immunoglobulin G; mRNA, messenger RNA; BNT162b2 and COMIRNATY, Pfizer BioNTech COVID-19 Vaccine; ECOG, Eastern Cooperative Oncology Group; mRNA-1273, Moderna COVID-19 Vaccine; PD-1, Programmed cell death protein 1; PD-L1, Programmed death-ligand 1; bAb, binding antibody; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; S1, spike protein subunit 1; S2, spike protein subunit 2; RBD, receptor-binding domain; COH04S1, City of Hope-developed COVID-19 vaccine; CAR T-cell, chimeric antigen receptor T-cell; MVA, modified vaccinia Ankara; CD-20, B-lymphocyte antigen CD20; HIV, human immunodeficiency virus; MM, multiple myeloma; EVUSHELD, tixagevimab and cilgavimab; CLL, chronic lymphocytic leukemia; GMC, geometric mean concentration; NVX-COV2373, Novavax COVID-19 Vaccine.