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

Multiple Myeloma Clinical Trial

Official title: 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

Status Completed

Clinical Trial 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.

Clinical Trial 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). ;

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms
• Leukemia
• Lymphoma
• Multiple Myeloma
• Neoplasms
• Solid Tumor Malignancy

• NCT number: NCT04847050
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: April 28, 2021
• Completion date: May 25, 2023