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 Boost...

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT04847050

Collaborator

(none)

220

Enrollment

Location

Arms

33.9

Anticipated Duration (Months)

6.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

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 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 2 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 an additional booster. 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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Malignancy Hematologic Malignancy Leukemia Lymphoma Multiple Myeloma	Biological: mrna 1273 injection	Phase 2

Detailed Description

Background:

Cancer patients are at increased risk from COVID-19 infection fatality due to underlying malignancy, treatment-related immunosuppression, or increased number of comorbidities.
In solid tumor patients, treatment with immune checkpoint inhibitor has been considered a potential predictor for severe disease. Similarly, patients with hematologic malignancies (acute leukemia, lymphoma, stem cell transplant) are the most immunosuppressed among all cancer patients and are known to have an increased risk for complications associated other respiratory viral infections.
ModernaTX, Inc. is using its mRNA-based technology to develop a novel lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA)-based vaccine against SARS-CoV-2 (mRNA-1273).
Preliminary clinical data from 1273 phase I study indicates that all 45 patients tested at doses 25, 100 and 200 mcg demonstrated antibodies after one dose and that 8 volunteers had neutralizing antibody.
Recently reported data shows that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology.

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-naive
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 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-naive 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 IgG antibodies against the SARS-CoV-2 nucleocapsid and spike (S) proteins

Eligibility:

Participants must have histologically or cytologically confirmed solid tumor; or confirmed diagnosis of acute leukemia (myeloid (AML) or lymphoid (ALL); multiple myeloma; or lymphoma, or post allogeneic stem cell transplantation (for any indication)
Age >=18 years
Participants with known history of SARS-CoV-2 infection or within 14 days of known exposure to someone with known SARS CoV2 infection COVD-19 are excluded
Participants with known hypotension, uncontrolled chronic pulmonary or cardiovascular disease are excluded
Participants with a history of anaphylaxis, urticaria, or other significant adverse reaction after receipt of vaccine are excluded

Design

This is an open-label, multicenter, phase II, clinical trial.
Up to 220 subjects will be enrolled.
For the vaccine naive cohorts we plan to enroll 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 (beyond physiologic dosing, if needed) and 60 participants with leukemia, lymphoma, multiple myeloma and patients post-allogeneic stem cell transplant. Participants will be enrolled based on their perceived risk of immunosuppression. Subjects will receive an IM injection (0.5 mL) of mRNA-1273 on Days 1 and 29 in the deltoid muscle and will be followed through 12 months post second vaccination (Day 394).
For the vaccine booster cohorts we plan to enroll 20 participants with solid tumor malignancies who have initiated PD1/PDL1 treatment, 20 participants with lymphocytic leukemia who are not on therapy, 20 participants with lymphocytic leukemia who are on BTK inhibitor therapy, 30 participants on CART cell therapy, 20 participants post allogeneic stem cell transplant, 20 participants with other hematologic malignancies and 10 participants with any solid tumor. Subjects will receive an IM injection (0.5 mL) of mRNA-1273 on Day 1 in the deltoid muscle and will be followed through 12 months post vaccination. Participants may receive up to 2 booster doses inclusive of any received prior to enrollment on study.
The duration of the entire study is anticipated to be 16 months (from start of screening to last subject last visit).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

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

Actual Study Start Date :

Apr 28, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Feb 25, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 100 mcg (0.5 mL) mRNA-1273 injection (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	Biological: mrna 1273 injection A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29 for vaccine naive cohorts or on Day 1 for vaccine booster cohorts. Participants may receive up to 2 booster injections on study
Experimental: 2 100 micrograms (0.5 mL) mRNA-1273 injection on D1	Biological: mrna 1273 injection A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29 for vaccine naive cohorts or on Day 1 for vaccine booster cohorts. Participants may receive up to 2 booster injections on study

Arm

Intervention/Treatment

Experimental: 1

100 mcg (0.5 mL) mRNA-1273 injection (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

Biological: mrna 1273 injection

A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29 for vaccine naive cohorts or on Day 1 for vaccine booster cohorts. Participants may receive up to 2 booster injections on study

Experimental: 2

100 micrograms (0.5 mL) mRNA-1273 injection on D1

Biological: mrna 1273 injection

Outcome Measures

Primary Outcome Measures

Safety and reactogenicity of MRNA-1273 vaccine [14 months]
-Solicited local and systemic Adverse Reactions (ARs) through 7 days after each injection. -Unsolicited AEs through 28 days after each injection. -SAEs throughout the entire study period. - Vital sign measurements and physical examination findings.
Safety and reactogenicity of MRNA-1273 of a booster vaccination [14 months]
-Solicited local and systemic Adverse Reactions (ARs) through 7 days after injection. -Unsolicited AEs through 28 days after injection. - SAEs throughout the entire study period. - Vital sign measurements and physical examination findings
Assess immunogenicity of m-RNA 1273 administered in 2 doses [14 months]
- 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 PD-1/PDL-1 inhibitor for treatment of a solid tumor - Titer or level of SARS-CoV-2-specific binding antibody (bAb) measured by ELISA on Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394.

Secondary Outcome Measures

immunogenicity of mrna-1273 vaccine as assessed by neutralizing antibody (nAb) [14 months]
For Vaccine Naive Arm: Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394 and for Booster Arm: Day 1, Day 29, Day 57, Day 180, and Day 360: -Titer or Level of SARS-CoV-2-specific neutralizing antibody (nAb) -Seroconversion due to vaccination as measured by an increase of SARS-CoV-2-specific nAb titer or level defined as -For subjects with no detectable antibody titer (< LOD) at baseline: post-vaccination titer = LLOQ -For subjects with a positive baseline titer (> LOD): post-vaccination titer = 4 times the LLOQ -For subjects with a baseline titer = LLOQ: post-vaccination titer = a 4-fold rise compared with baseline titer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

Participants must meet all the inclusion criteria in order to be eligible to participate in the study.

Participants must have one of the following:

Histologically or cytologically confirmed solid tumor receiving a standard of care PD1/PDL1 inhibitor for treatment of their solid tumor (inclusive of Hodgkin Lymphoma and Primary Mediastinal B-Cell Lymphoma particpants 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
AST(SGOT)/ALT(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

Glomerular Filtration Rate minimum will be required as follows: >30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.

Participants with history of human immunodeficiency virus (HIV) may enroll
Participants with history of chronic hepatitis B virus (HBV) must be on suppressive therapy (if indicated) with undetectable viral load.
Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured with an undetectable HCV viral load. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
A negative urine/serum pregnancy test for females of childbearing potential. The effects of mRNA-1273 Vaccine on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for 30 days after the last study treatment.

Note: A female is considered to be of childbearing potential if she has experienced menarche and is not permanently sterile (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation) or postmenopausal (postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause and with a serum follicle-stimulating hormone test result in the postmenopausal range).

Effective methods of contraception:

Intrauterine device.
Stable dose of hormonal birth control, such as those listed below, for at least 3 months prior to enrollment.
Hormonal contraceptive tablets.
Injectable hormonal contraceptives.
Implanted hormonal contraceptives.
Cutaneous contraceptive patches.
Intravaginal hormonal contraceptive rings.

At least 1 barrier method. Effective barrier methods for use in this study are:

Male or female condom.
Diaphragm.
Creams or gels that contain a chemical to kill sperm

If a female patient has a male participant who has had surgery to prevent pregnancy (vasectomy), that will be considered evidence of effective contraception.

Ability to understand and the willingness to sign a written informed consent document.
CLL participants undergoing BTKi treatment interruption: Must be receiving treatment with a BTKi for (Bullet)6 months prior to vaccination and be willing to hold their treatment for up to 3 weeks around the time of vaccination.

EXCLUSION CRITERIA:

All participants meeting any of the exclusion criteria at baseline will be excluded from study participation.

Within 14 days of known exposure to someone with confirmed SARS CoV2 infection or 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 EUA vaccine for COVID19, but all others must have received 2 doses) at least 4 weeks prior to vaccination on protocol. PatientParticipants will be allowed to enroll if they have already received a booster dose 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.
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.
Has received an inactivated vaccine within 14 days before the first dose of study treatment.
Have major surgical procedures within 28 days or non-study-related minor procedures within 7 days before the first dose of study treatment. In all cases, the participant must be sufficiently recovered and stable before treatment administration.
History of severe allergic reactions to any components of the study treatment.
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).

The following are exceptions to this criterion:

Vitiligo or alopecia
Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition such as eczema or celiac disease that does not require systemic therapy
Celiac disease controlled by diet alone.
History of primary immunodeficiency, allogenic solid organ transplantation, or tuberculosis.
Solid tumor participants with a history of leptomeningeal carcinomatosis.
Has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe or ongoing interstitial lung disease (ILD), serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the participant to give written informed consent.
Active tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice).
History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has involvement in the planning and/or conduct of the study.
Female who is pregnant or breastfeeding
Male or female participant of reproductive potential who are not willing to employ effective birth control from screening to 30 days after the last dose of study treatment.