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

Phase 2

Completed

• Conditions: Leukemia; Multiple Myeloma; Hematologic Malignancy; Lymphoma; Solid Tumor Malignancy
• Interventions: Biological: Messenger ribonucleic acid (mRNA)-1273 Vaccine; Biological: Messenger ribonucleic acid (mRNA)-1273 Vaccine Booster; Diagnostic Test: ECG; Other: Antibiotics; Other: Anti-viral agents; Other: Anti-fungal agent; Other: Anti-emetics

• Registration Number: NCT04847050
• Lead Sponsor: National Cancer Institute (NCI)

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.

Detailed Description

Design of the Study:

This is an open-label, multicenter clinical trial designed to evaluate the safety, reactogenicity and primary immunogenicity of the messenger ribonucleic acid (mRNA)-1273 vaccine administered in 2 doses, 28 days apart, in participants who have hematological malignancy and are immunosuppressed due to their disease and/or treatment or receiving a Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PDL-1) inhibitor for treatment of a solid tumor can be associated with appropriately high rates of development of neutralizing antibodies of mRNA-1273. The trial will also evaluate the safety, reactogenicity and immunogenicity after administration of additional booster doses of the vaccine.

Study Phase:

Study Population:

For the vaccine-na(SqrRoot) ve cohorts, up to 80 participants will be enrolled.

* 20 participants with solid tumor malignancies who have initiated PD1/PDL1 inhibitor therapy as part of standard of care and are deemed to have a stable regimen without the need for any immunosuppressive therapy or corticosteroids.

* 60 participants with leukemia, lymphoma, multiple myeloma and participants post-allogeneic stem cell transplant will be enrolled based on their perceived risk of immunosuppression.

For the previously-vaccinated (also known as "booster") cohorts, up to 140 participants will be enrolled for booster injections. All participants on the vaccine-na(SqrRoot) ve cohorts will have the option of receiving boosters; however, they will not count towards the maximum accrual goal for each of the booster groups. Note: All participants will be eligible to receive up to three (3) booster doses of vaccine on study.

* 20 participants with solid tumor malignancies who have initiated PD1/PDL1 inhibitor therapy as part of standard of care and are deemed to have a stable regimen without the need for any immunosuppressive therapy or corticosteroids.

* 20 participants with chronic lymphocytic leukemia who are not currently on any therapies

* 20 participants with chronic lymphocytic leukemia who are on Bruton's tyrosine kinase (BTK) inhibitor therapy alone

* 30 participants with any chimeric antigen receptor (CAR) T Cell therapy for a hematologic malignancy

* 20 participants post-allogeneic stem cell transplant

* 20 participants with other hematologic malignancies

* Up to 10 participants with any solid tumor who are not otherwise eligible for any of the other cohorts

Number of Sites: 2

Description of Study Product or Intervention:

mRNA-1273 Injection (Drug Product) is an lipid nanoparticles (LNPs) dispersion containing a single mRNA sequence (Drug Substance) that encodes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S glycoprotein stabilized in the prefusion conformation. The mRNA-1273 Drug Substance is combined with a mixture of 4 lipids common to the Moderna's mRNA vaccine platform: SM-102 (a custom-manufactured, ionizable lipid) and 3 commercially available lipids, cholesterol, distearoylphosphatidylcholine (DSPC), and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000-DMG) (https://doi.org/10.1038/s41587-020- 00807-1). mRNA-1273 Injection is provided as a sterile solution for injection, white to off white dispersion in appearance.

Presentation: mRNA-1273 Injection is provided as a sterile solution for injection at a concentration of 0.2 mg/mL in 20 mM trometamol (Tris) buffer containing 87 mg/mL sucrose and 4.3 mM acetate, at potential hydrogen (pH) 7.5. mRNA-1273 Injection is presented in 10R USP Type I borosilicate glass vials with PLASCAP vial seal containing a 20 mm FluroTec-coated plug stopper and has a 6.3 mL nominal fill volume. This vial may be used for more than one participant.

mRNA-1273 Injection must be stored frozen at -15 degrees C to -25 degrees C until thawed for use and then stored refrigerated at 2 degrees C to 8 degrees C for up to 30 days (once thawed it must not be refrozen)

Each dose of 100 mcg (0.5 mL) will be administered via IM injection into the deltoid muscle on Days 1 and 29 (+/- 3 days) for the vaccine-na(SqrRoot) ve cohorts. Up to 3 additional (booster) doses of the vaccine may also be administered.

Study Objectives:

Primary:

* To evaluate the safety and reactogenicity of the mRNA-1273 vaccine administered in 2 doses, 28 days apart, in participants who have a hematological malignancy and are immunosuppressed due to their disease and/or treatment, or receiving a PD-1/PDL-1 inhibitor for treatment of a solid tumor for patients who are vaccine-na(SqrRoot) ve

* To evaluate the safety and reactogenicity of booster doses of mRNA-1273 vaccine administered to participants who have previously received an mRNA or alternative vaccine regimen

* To evaluate the safety and reactogenicity of booster doses of mRNA-1273 administered to participants with chronic lymphocytic leukemia (CLL) who are either off treatment or are engaging in a 3-week BTK inhibitor interruption to enhance vaccine immunogenicity

* To assess the immunogenicity of mRNA-1273 in participants with cancer, as assessed by the titer or level of specific binding antibody (bAb)

Secondary:

* To evaluate the immunogenicity of the mRNA-1273 vaccine administered in 2 doses 28 days apart, as assessed by the titer or level of neutralizing antibody (nAb) in the vaccine-na(SqrRoot) ve cohorts

* To evaluate the immunogenicity of booster doses of mRNA-1273 vaccine administered to participants who have previously been vaccinated against SARS-CoV2 with any prior vaccine regimen. as assessed by the titer or level of neutralizing antibody (nAb)

Exploratory:

* To assess immune responses against the SARS-CoV-2 nucleocapsid and spike proteins

* To evaluate salivary measurement of immunoglobulin G (IgG) antibodies against the SARS-CoV-2 nucleocapsid and spike (S) proteins

Duration of Individual Participant Participation:

The duration for each individual participation is approximately 14 months (from first contact to last visit).

Study Duration:

Study duration is anticipated to be 16 months (from start of screening to last Participant/last visit).

Study Timeline

• Study First Submitted: 2021-04-14
• Study First Submitted QC: 2021-04-14
• Study First Posted: 2021-04-15
• Study Start: 2021-04-28
• Primary Completion: 2023-05-25
• Study Completion: 2023-05-25
• Disposition First Submitted: 2024-05-21
• Results First Submitted: 2024-07-01
• Status Verified: 2024-08
• Results First Submitted QC: 2024-08-05
• Last Update Submitted: 2024-08-05
• Results First Posted: 2024-08-27
• Disposition First Posted: 2024-08-27
• Last Update Posted: 2024-08-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 messenger ribonucleic acid (mRNA)	ECG	100 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 1 messenger ribonucleic acid (mRNA)	Anti-fungal agent	100 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)	ECG	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Arm 1 messenger ribonucleic acid (mRNA)	Antibiotics	100 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 1 messenger ribonucleic acid (mRNA)	Anti-emetics	100 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)	Antibiotics	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Arm 1 messenger ribonucleic acid (mRNA)	Messenger ribonucleic acid (mRNA)-1273 Vaccine	100 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)	Messenger ribonucleic acid (mRNA)-1273 Vaccine	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Arm 1 messenger ribonucleic acid (mRNA)	Messenger ribonucleic acid (mRNA)-1273 Vaccine Booster	100 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 1 messenger ribonucleic acid (mRNA)	Anti-viral agents	100 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)	Anti-emetics	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Arm 2 messenger ribonucleic acid (mRNA)	Anti-viral agents	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1
Arm 2 messenger ribonucleic acid (mRNA)	Anti-fungal agent	100 micrograms (0.5 mL) messenger ribonucleic acid (mRNA) injection on day (D)1

Primary Outcome Measures

Name	Time	Method
Number of Participants With Reactogenicity of Messenger Ribonucleic Acid (mRNA)-1273 Vaccine: Initial Phase	End of 15-minute observation period following each vaccination on Day 1 and Day 29	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.
Number of Participants With Reactogenicity of Messenger Ribonucleic Acid (mRNA) -1273 of a Booster Vaccination: Booster Phase	End of 15-minute observation period following each vaccination on Day 1 and Day 29	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.
Number of Participants With Grades 1-5 Solicited (Expected) and/or Unsolicited (Unexpected) Adverse Events (AE's): Booster Phase	7 and 28 days after each injection and throughout the entire study period, a median of 19.5 months	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.
Number of Participants Who Had Vital Signs Performed Prior to 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)	Vital signs: weight, temperature, heart rate/pulse, respirations, and blood pressure will be performed prior to each vaccine.
Number of Participants With Grades 1-5 Solicited (Expected) and/or Unsolicited (Unexpected) Adverse Events (AE's): Initial Phase	7 and 28 days after each injection and throughout the entire study period, a median of 19.5 months	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.
Immunogenicity of Messenger Ribonucleic Acid (mRNA) Titers - 1273 Administered in 2 Doses in the Initial Phase	Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394	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.

Secondary Outcome Measures

Name	Time	Method
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 samples with a neutralizing response (defined as neutralization assay above 30%) will be reported. Immunogenicity of mRNA-1273 vaccine was assessed for Vaccine Naive Arm 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. Assessment was performed on 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	Number of samples with a neutralizing response (defined as neutralization assay above 30%) will be reported. Participants would receive one to two vaccine boosters. Analysis of timepoints after booster 1 and booster 2 are reported collectively. Immunogenicity of mRNA-1273 vaccine was assessed for Booster Arm in participants with hematologic malignancy with or without ongoing immune suppression and participants with solid tumor receiving programmed death-1 (PD-1)/programmed death-ligand 1 inhibitor (PD-L1) inhibitors: 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	Immunogenicity of mRNA 1273 administered in 2 doses was assessed by titer or level of specific binding antibody (bAb), in participants with hematologic malignancy with or without ongoing immune suppression and patients with solid tumor receiving programmed death-1 (PD-1)/programmed death-ligand 1 inhibitor (PD-L1) inhibitors. 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 57, Day 180, and Day 360. Participants received one or two vaccine boosters. Analysis of timepoints after booster 1 and booster 2 are reported collectively.

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States