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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...

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ClinicalTrials.gov Identifier: NCT04847050
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : July 1, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : April 28, 2021
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : February 25, 2024


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, 100 mcg (0.5 mL) mRNA-1273 injection (IM) no less than 4 weeks after day 29
Biological: mRNA-1273
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
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




Primary Outcome Measures :
  1. Safety and reactogenicity of MRNA-1273 vaccine [ Time Frame: 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.

  2. Safety and reactogenicity of MRNA-1273 of a booster vaccination [ Time Frame: 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

  3. Assess immunogenicity of m-RNA 1273 administered in 2 doses [ Time Frame: 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 :
  1. immunogenicity of mrna-1273 vaccine as assessed by neutralizing antibody (nAb) [ Time Frame: 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04847050


Contacts
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Contact: Marissa B Mallek, R.N. (240) 760-7498 marissa.mallek@nih.gov
Contact: Elad Sharon, M.D. (240) 276-6102 sharone@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
United States, Washington
Fred Hutchinson Cancer Research Center Not yet recruiting
Seattle, Washington, United States, 28104
Contact: Joshua Hill    206-667-6504    jahill3@fredhutch.org   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Elad Sharon, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04847050    
Other Study ID Numbers: 10000115
000115-C
First Posted: April 15, 2021    Key Record Dates
Last Update Posted: July 1, 2022
Last Verified: April 28, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All 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 dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
mRNA-1273 vaccine
moderna
SARS-CoV-2
booster shot
Additional relevant MeSH terms:
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Neoplasms
Multiple Myeloma
Hematologic Neoplasms
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site