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...
- - 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.
- 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.
- 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
- 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)
- 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
- 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)
- 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
- 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
- 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).
Trial Phase Phase II
Trial Type Prevention
National Cancer Institute
- Primary ID 10000115
- Secondary IDs NCI-2021-03438, 000115-C
- Clinicaltrials.gov ID NCT04847050