Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04847050
Recruitment Status : Recruiting
First Posted : April 15, 2021
Last Update Posted : June 10, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Tracking Information
First Submitted Date  ICMJE April 14, 2021
First Posted Date  ICMJE April 15, 2021
Last Update Posted Date June 10, 2021
Actual Study Start Date  ICMJE April 28, 2021
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2021)
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 14, 2021)
  • 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 are receiving either an immunosuppressive regimen of therapy for the treatment of a hematological malignancy or 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 197, and Day 365.
  • 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2021)
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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 14, 2021)
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 197, and Day 365.-Seroconversion due to vaccination on Day 29, Day 36, Day 57, Day 197, and Day 365 as measured by an increase of SARS-CoV-2-specific nAb titer or level either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.

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
  • To assess the immunogenicity of COVID-19 vaccine, mRNA-1273, administered in 2 doses 28 days apart, as assessed by the 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

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)

Exploratory:

  • To assess immune responses against the SARS-CoV-2 nucleocapsid and spike proteins
  • To evaluate salivary measurement of IgG

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
  • ECOG performance status <2
  • Participants must have adequate organ and bone marrow function
  • 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 who have had prior administration of an investigational coronavirus (e.g. SARS-CoV-2, SARS-CoV, MERS-CoV) vaccine 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 120 subjects will be enrolled.
  • For this trial, on the solid tumor cohort, we plan to enroll 60 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).
  • For this trial, on the hematologic malignancy cohort, we plan to enroll 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).
  • The duration of the entire study is anticipated to be 16 months (from start of screening to last subject last visit).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • Solid Tumor Malignancy
  • Hematologic Malignancy
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
Intervention  ICMJE Biological: mRNA-1273
A rapid response, proprietary messenger RNA (mRNA)-based vaccine platform. 100 mcg administered IM on Day 1 and 29
Study Arms  ICMJE Experimental: 1
100 microgram (0.5 mL) mRNA-1273 injection on D1 and 29
Intervention: Biological: mRNA-1273
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 14, 2021)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 25, 2023
Estimated Primary Completion Date January 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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 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.

    • 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 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-allogeneic transplant participants who have not converted to donor chimerism.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marissa B Mallek, R.N. (240) 760-7498 marissa.mallek@nih.gov
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04847050
Other Study ID Numbers  ICMJE 10000115
000115-C
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elad Sharon, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 7, 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP