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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

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ClinicalTrials.gov Identifier: NCT04847050
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : May 4, 2021
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. The COVID-19 Vaccine from Moderna has obtained an emergency use authorization from the FDA. The vaccine has been proven to reduce infections with the virus that causes COVID-19, and it has already been given to millions of people around the world.

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. It will be injected into a muscle in the arm on Days 1 and 29. Participants will have a follow-up phone call on Day 8 after the first dose. They will be followed for 12 months after the second dose.

Participants will have study visits at the Clinical Center on Days 1 and 29 to get the COVID-19 vaccine from Moderna. Patients will then be asked to come back for visits about 1 week and 1 month after the second dose. Patients will need to come back for visits 6 months and 1 year after the second vaccine dose to check to see how long the vaccine offers protection.

Some visits will last up to a few hours, but most will be significantly shorter.

Participants will give blood and saliva samples for research.

Participation will last about 13 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 : 120 participants
Allocation: N/A
Intervention Model: Single Group 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
Actual Study Start Date : April 28, 2021
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : February 25, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1
100 microgram (0.5 mL) mRNA-1273 injection on D1 and 29
Biological: mRNA-1273
A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29




Primary Outcome Measures :
  1. 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.

  2. 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.- Safety laboratory abnormalities at Day 29 and Day 57.- Vital sign measurements and physical examination findings.


Secondary Outcome Measures :
  1. immunogenicity of mrna-1273 vaccine as assessed by neutralizing antibody (nAb) [ Time Frame: 14 months ]
    -Titer or level of SARS-CoV-2-specific neutralizing antibody (nAb) on Day 1, Day 29, Day 36, Day 57, Day 209, and Day 394.-Seroconversion due to vaccination on Day 29, Day 36, Day 57, Day 209, and Day 394 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-vaccinationtiter >= LLOQ-For subjects with a positive baseline titer (> LOD): post-vaccinationtiter >= 4 times the LLOQ-For subjects with a baseline titer >= LLOQ: post-vaccinationtiter >= a 4-fold rise compared with baseline titer



Information from the National Library of Medicine

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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 Medistinal B-Cell Lymphoma patients 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)
    • Age >=18 years.
    • ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 50%).
    • 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-Grade 3 or lower, corresponding to a minimum value of 500 cells per mcL
  • Absolute neutrophil count-Grade 3 or lower, corresponding to a minimum value of 500 cells per mcL
  • Platelets-Grade 3 or lower, corresponding to a minimum value of 50,000 cells per mcL
  • Total bilirubin-Grade 2 or lower, corresponding to a maximum value of 3.0 x upper limit of normal
  • AST(SGOT)/ALT(SGPT)-Grade 2 or lower, corresponding to a maximum value of 5.0 x upper limit of normal
  • Creatinine-Grade 2 or lower, corresponding to a 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 patients with elevated creatinine)-For patients 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 hematologic malignancies with history of treated central nervous disease, must have had at least 2 consecutive lumbar punctures with no evidence of clinically active central nervous system disease.
  • Participants with history of human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy
  • 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 partner 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.

EXCLUSION CRITERIA:

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

  • Known history of SARS-CoV-2 infection or 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.
  • Prior administration of an investigational coronavirus (e.g., SARS-CoV-2, SARS-CoV, MERS-CoV) vaccine.
  • Current treatment with investigational agents for prophylaxis against COVID-19.
  • Known history of hypotension or systolic blood pressure < 85 mm Hg at the Screening Visit (Day 0).
  • 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 patient 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 patient must be sufficiently recovered and stable before treatment administration.
  • Diagnostic Assessments

    • Must not have experienced a > Grade 3 immune related AE while receiving immunotherapy. Note: Participants with endocrine AEs of any grade are permitted to enroll if they are stable while maintained on appropriate replacement therapy and are asymptomatic.
    • 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 patient to give written informed consent.
    • Active infection including 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 patient of reproductive potential who are not willing to employ effective birth control from screening to 30 days after the last dose of study treatment.
    • Post-allogenic transplant participants who have not fully converted to donor chimerism, still on immunosuppressants such as cyclosporine, mycophenolate mofetil, tacrolimus (FK506), or participants with acute or chronic GVHD will be excluded.

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

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      
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: May 4, 2021
Last Verified: April 30, 2021

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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
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