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
2 other identifiers
interventional
19
1 country
1
Brief Summary
Background: Coronavirus disease (COVID-19) is a viral infection. It has spread rapidly across the globe. It has overwhelmed health systems. Researchers are concerned that it may undo years of progress in the reduction of cancer-specific death. They want to test a vaccine that might protect people with cancer from COVID-19. Objective: To test the safety and efficacy of a vaccine using messenger ribonucleic acid (mRNA)-1273 that may protect people with cancer from COVID-19. Eligibility: Adults ages 18 and older who have a solid tumor or blood cancer and who may benefit from a vaccine that might prepare their immune system for fighting and preventing infection from COVID-19. Patients with solid tumors must be receiving treatment with an immunotherapy agent. Design: Participants will be screened with a medical history, medicine review, and physical exam. They will have blood tests. They will have a pregnancy test if needed. Participants will get 2 doses of the mRNA-1273 vaccine if they have not been vaccinated already. It will be injected into a muscle in the arm on Days 1 and 29. They will be followed for 12 months after the second dose. Participants will have study visits at the Clinical Center on Days 1, 29, 36,57, 209, and 394. Some visits will last about 4-6 hours. Patients will be able to get up to 3 doses of mRNA-1273 as a booster on trial if they have already completed a primary series of a vaccine. Participants who have already received a booster dose of vaccine will be able to enroll to receive additional boosters. It will be injected into a muscle in the arm on Day 1. Participants will be followed for 12 months after their last booster injection. Participants who receive booster doses will have study visits at the Clinical Center on Days 1, 29, 57, 180 and 360. Participants will give blood and saliva samples for research. Participation will last about 16 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2021
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 14, 2021
CompletedFirst Posted
Study publicly available on registry
April 15, 2021
CompletedStudy Start
First participant enrolled
April 28, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 25, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
May 25, 2023
CompletedResults Posted
Study results publicly available
August 27, 2024
CompletedAugust 27, 2024
August 1, 2024
2.1 years
April 14, 2021
July 1, 2024
August 5, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Number of Participants With Grades 1-5 Solicited (Expected) and/or Unsolicited (Unexpected) Adverse Events (AE's): Initial Phase
Solicited (expected) local and systemic Adverse Reactions (ARs) through 7 days after each injection were assessed using the clinical abnormalities section of the Food and Drug Administration (FDA) -Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Unsolicited (unexpected) adverse events (AEs) through 28 days after each injection and serious adverse events (SAE's) throughout the entire study period were assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
7 and 28 days after each injection and throughout the entire study period, a median of 19.5 months
Number of Participants With Reactogenicity of Messenger Ribonucleic Acid (mRNA)-1273 Vaccine: Initial Phase
Reactogenicity of mRNA-1273 vaccine was assessed by physical examination findings following vaccination. A physical exam will be performed to assess general physical condition in the following areas: supraclavicular and axillary lymph nodes, cardiovascular, pulmonary, abdomen and skin and include an assessment of pain, tenderness, erythema, induration and warmth at the injection site, fever, chills, arthralgia/joint pain, malaise/fatigue, myalgia/body aches, headache, nausea, vomiting, and abdominal pain following vaccination.
End of 15-minute observation period following each vaccination on Day 1 and Day 29
Number of Participants With Grades 1-5 Solicited (Expected) and/or Unsolicited (Unexpected) Adverse Events (AE's): Booster Phase
Solicited (expected) local and systemic Adverse Reactions (ARs) through 7 days after each injection were assessed using the clinical abnormalities section of the Food and Drug Administration (FDA) -Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Unsolicited (unexpected) adverse events (AEs) through 28 days after each injection and serious adverse events (SAE's) throughout the entire study period were assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
7 and 28 days after each injection and throughout the entire study period, a median of 19.5 months
Number of Participants Who Had Vital Signs Performed Prior to Vaccine
Vital signs: weight, temperature, heart rate/pulse, respirations, and blood pressure will be performed prior to each vaccine.
Prior to each vaccine. Screening or Day 0 visit; Day 1, visit 1, vaccine dose 1; Day 29, visit 2, vaccine dose 2; Day 209 (6 months), visit 5 (+/- 28 days); and Day 394, visit 6 (+/- 28 days)
Immunogenicity of Messenger Ribonucleic Acid (mRNA) Titers - 1273 Administered in 2 Doses in the Initial Phase
Immunogenicity of mRNA 1273 administered in 2 doses was assessed by titer or level of specific binding antibody (bAb), in participants who have a hematological malignancy and are immunosuppressed due to their disease and/or treatment or receiving a programmed death-1 (PD-1)/programmed death-ligand 1 inhibitor for treatment of a solid tumor - Titer or level of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA) on Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394.
Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394
Number of Participants With Reactogenicity of Messenger Ribonucleic Acid (mRNA) -1273 of a Booster Vaccination: Booster Phase
Reactogenicity of mRNA-1273 of a booster vaccination was assessed by physical examination findings following vaccination. A physical exam will be performed to assess general physical condition in the following areas: supraclavicular and axillary lymph nodes, cardiovascular, pulmonary, abdomen and skin and include an assessment of pain, tenderness, erythema, induration and warmth at the injection site, fever, chills, arthralgia/joint pain, malaise/fatigue, myalgia/body aches, headache, nausea, vomiting, and abdominal pain following vaccination.
End of 15-minute observation period following each vaccination on Day 1 and Day 29
Secondary Outcomes (3)
Number of Neutralizing Antibody Samples - Initial Phase
For Vaccine Naive Arm: Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394
Number of Neutralizing Antibody Samples - Booster Phase
Day 1, Day 29, Day 57, Day 180, and Day 360
Immunogenicity of Messenger Ribonucleic Acid (mRNA) -1273 Levels Administered in 2 Doses in the Booster Phase
Day 1, Day 29, Day 57, Day 180, and Day 360
Other Outcomes (1)
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
From study product administration on Day 1 through 28 days after the last vaccination (through resolution); a median of 19.5 months.
Study Arms (2)
Arm 1 messenger ribonucleic acid (mRNA)
EXPERIMENTAL100 mcg (0.5 mL) messenger ribonucleic acid (mRNA)-1273 injection intramuscular (IM) on days 1 and 29; with option for subsequent booster dose(s), 100 mcg (0.5 mL) mRNA-1273 injection (IM) no less than 4 weeks after day 29
Arm 2 messenger ribonucleic acid (mRNA)
EXPERIMENTAL100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Interventions
A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered intramuscular (IM) on Day 1 and 29 for vaccine naive cohorts.
A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered intramuscular (IM) on Day 1 for vaccine booster cohorts. Participants may receive up to 3 booster injections on study.
Baseline (-28 days/Day 1); and Day 29 (+/- 3 days).
Use of prophylactic antibiotics is recommended according to institutional standards.
Use of prophylactic antiviral agents is recommended according to institutional standards.
Use of prophylactic antifungal agents is recommended according to institutional standards.
Use of prophylactic anti-emetics is recommended according to institutional standards.
Eligibility Criteria
You may qualify if:
- Participants must have one of the following:
- Histologically or cytologically confirmed solid tumor receiving a standard of care programmed cell death protein 1 (PD1)/Programmed death-ligand 1 (PDL1) inhibitor for treatment of their solid tumor (inclusive of Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma participants receiving PD1/PDL1 inhibitors as standard of care therapy)
- Confirmed diagnosis of acute leukemia (myeloid (AML) or lymphoid (ALL) or other acute leukemia; multiple myeloma; Waldenstrom macroglobulinemia
- Confirmed diagnosis of lymphoma, including small lymphoblastic lymphoma (i.e.,chronic lymphocytic leukemia)
- Be post allogeneic stem cell transplantation (for any indication)
- Be an adult patient (aged 18 or older) with any malignancy who does not fit any of the above categories
- Age \>=18 years.
- History of adequate organ and marrow function on a recent laboratory assessment (within 4 weeks of administration of vaccine), as defined below:
- Absolute lymphocyte count-Minimum value of 200 cells per mcL
- Absolute neutrophil count-Minimum value of 500 cells per mcL
- Platelets-Minimum value of 25,000 cells per mcL
- Total bilirubin-Maximum value of 3.0 x upper limit of normal
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine transaminase ALT serum glutamic-pyruvic transaminase (SGPT)-Maximum value of 5.0 x upper limit of normal
- Creatinine-Maximum value of 3.0 x upper limit of normal (if elevated, use of creatinine calculated clearance will be necessary, as below)
- Creatinine clearance (only necessary for participants with elevated creatinine)-For participants with Chronic Kidney Disease, a calculated
- +21 more criteria
You may not qualify if:
- Within 14 days of known exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease (COVID-19).
- Acutely ill or febrile 24 hours prior to or at the Screening Visit (Day 0). Fever is defined as a body temperature greater than or equal to 38.0 degrees C/100.4 degrees F. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled at the discretion of the investigator.
- Participants on the vaccine na(SqrRoot) ve arms cannot have received any doses of the COVID-19
- vaccine.
- Participants who have not completed a standard vaccination series due to initiation of vaccination in a foreign location (e.g., single dose of Astra-Zeneca vaccine or a similar situation) may be enrolled after discussion with the principal investigator.
- Participants on the booster arms must have received all doses of their initial COVID-19 vaccine (Participants vaccinated with the Janssen vaccine must have received the single dose of that Emergency Use Authorization (EUA) vaccine for COVID19, but all others must have received 2 doses) at least 4 weeks prior to vaccination on protocol. Participants will be allowed to enroll if they have already received booster doses of vaccine prior to enrolling on the protocol at least four weeks prior to vaccination on protocol. In this case, the protocol will administer a single booster dose of vaccination. Documentation will be required.
- Known diagnosis of chronic pulmonary disease (e.g., chronic obstructive pulmonary disease, asthma) that is not controlled.
- Chronic cardiovascular disease that is not controlled.
- Participants with a history of myocarditis (inflammation of the heart) or pericarditis (inflammation of the pericardium)
- History of anaphylaxis, urticaria, or other significant adverse reaction requiring medical intervention after receipt of a vaccine.
- Bleeding disorder considered a contraindication to intramuscular (IM) injection or phlebotomy.
- Participated in an interventional clinical trial with an investigational agent within 28 days prior to the Screening Visit (Day 0) or plans to do so while participating in this study. The site investigator may enroll a participant on the trial earlier than 28 days if enough time has passed to ensure that at least five half-lives have occurred.
- Prior/Concomitant Therapy
- Has received prior radiotherapy within 14 days before the first dose of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 7-day washout is permitted for palliative radiation (less than or equal to 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- Has received a live vaccine within 30 days before the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist (registered trademark)) are live attenuated vaccines and are not allowed.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James Gulley
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James Gulley, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
April 14, 2021
First Posted
April 15, 2021
Study Start
April 28, 2021
Primary Completion
May 25, 2023
Study Completion
May 25, 2023
Last Updated
August 27, 2024
Results First Posted
August 27, 2024
Record last verified: 2024-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
- Access Criteria
- Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).