AL Amyloidosis, Chronic Lymphocytic Leukemia, Multiple Myeloma
Conditions
Brief summary
To determine whether protective antibody levels increase after booster dosing with the Moderna COVID-19 vaccine in patients diagnosed with Hematologic Malignancies who have low antibody levels after a prior first vaccination with any of the SARS-CoV2 vaccines that were authorized for use in the USA. Researchers will also assess whether the booster dosing with the Moderna COVID-19 vaccine is safe in patients with multiple myeloma, amyloidosis, or other blood cancers.
Detailed description
The specific hypothesis being tested is that it may be possible to induce a protective humoral immune response with a booster dose of the Moderna COVID-19 vaccine in patients with hematologic malignancies who did not have an adequate response to first vaccination with any of the available COVID-19 vaccines. To test this hypothesis, t a Phase II singlestage trial in which patients with a negative or weak positive anti-SARS-CoV2 IgG antibody test (defined as \<1.00 S/CO and 1.00-1.99 S/CO, respectively) will receive a single standard dose of the Moderna COVID-19 vaccine intramuscularly, and then have anti-SARS-CoV2 IgG antibody levels checked 28 days (+/-3 days) later.
Interventions
DRUGA single booster dose of the Moderna mRNA COVID-19 vaccine
All participants will receive a single dose of the Moderna mRNA COVID-19 vaccine administered intramuscularly. This is an open label, non-randomized trial.
Sponsors
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, aged 18 years of age or older 4. Previously diagnosed with MM/AL amyloidosis (Cohorts 1 or 3) or other hematologic malignancy (Cohorts 2 or 3). 5. Previously received any one of the available COVID-19 vaccines (between 4 and 36 weeks prior to enrollment) 6. Anti-SARS-CoV2 IgG antibody titer of results less than 1.0 units (Cohorts 1 and 2), or 1.0-1.99 units (Cohort 3). Antibody titers will be measured within 14 days of enrollment. 7. If currently receiving potentially immunosuppressive anti-neoplastic therapy for their underlying hematologic condition, a two-week interruption in therapy before and after the booster dose of vaccine is ENCOURAGED BUT NOT REQUIRED (physician discretion).-
Exclusion criteria
1. Daily corticosteroids at a dose equivalent to Prednisone 20 mg/day or greater during the period two weeks before enrollment to the trial. Intermittent steroid dosing at or above this level is permitted (i.e., weekly dexamethasone dosing as part of myeloma therapy) 2. History of previous severe reaction to any available COVID-19 vaccine (defined as any Grade 3 or higher reaction) 3. Febrile illness within 3 days of booster dosing. 4. Documented SARS-CoV2 infection within 2 weeks of enrollment. 5. Less than 3 months post-autologous or allogeneic stem cell transplant (NOTE: transplant between initial standard vaccine administration and enrollment is NOT otherwise grounds for exclusion from participation).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion. | 28 days (+/- 3 days) following a booster dose of the Moderna mRNA COVID-19 vaccine | Anti-SARS-CoV2 IgG antibody seroconversion from negative to positive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Observed Rate of STRONG POSITIVE Anti-SARS-CoV2 Antibody Response | measured 28 days (+/- 3 days) following a booster dose of the Moderna COVID-19 vaccine. | A STRONG POSITIVE response is defined in this trial as an anti-SARS-CoV2 IgG antibody titer of at least 2 S/CO 28 days (+/- 3 days) following vaccine administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Multiple myeloma and amyloidosis patients who did not develop an anti-spike antibody titer of \>1 S/CO after prior COVID-19 vaccination. | 52 |
| Cohort 2 Patients with other hematologic malignancies who did not develop an anti-spike antibody titer of \>1 S/CO after prior COVID-19 vaccination. | 51 |
| Cohort 3 Patients with multiple myeloma, amyloidosis, or other hematologic malignancy who had a weak positive response to prior COVID-19 vaccine, defined as an anti-spike antibody titer of 1-2 S/CO. | 16 |
| Total | 119 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 37 Participants | 33 Participants | 6 Participants | 76 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 18 Participants | 10 Participants | 43 Participants |
| Age, Continuous | 68 years | 68 years | 63.5 years | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 2 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 49 Participants | 43 Participants | 12 Participants | 104 Participants |
| Sex: Female, Male Female | 25 Participants | 18 Participants | 6 Participants | 49 Participants |
| Sex: Female, Male Male | 27 Participants | 33 Participants | 10 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 52 | 4 / 50 | 2 / 16 |
| other Total, other adverse events | 48 / 52 | 47 / 50 | 16 / 16 |
| serious Total, serious adverse events | 0 / 52 | 0 / 50 | 1 / 16 |
Outcome results
Primary
Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion.
Anti-SARS-CoV2 IgG antibody seroconversion from negative to positive.
Time frame: 28 days (+/- 3 days) following a booster dose of the Moderna mRNA COVID-19 vaccine
Population: Participants who received a single dose of the Moderna mRNA COVID-19 vaccine administered intramuscularly.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion. | 29 Participants |
| Cohort 2 | Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion. | 28 Participants |
| Cohort 3 | Observed Response Rate of Anti-SARS-CoV2 Antibody Seroconversion. | 0 Participants |
Secondary
Observed Rate of STRONG POSITIVE Anti-SARS-CoV2 Antibody Response
A STRONG POSITIVE response is defined in this trial as an anti-SARS-CoV2 IgG antibody titer of at least 2 S/CO 28 days (+/- 3 days) following vaccine administration
Time frame: measured 28 days (+/- 3 days) following a booster dose of the Moderna COVID-19 vaccine.
Population: Participants who received a single dose of the Moderna mRNA COVID-19 vaccine administered intramuscularly.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Observed Rate of STRONG POSITIVE Anti-SARS-CoV2 Antibody Response | 27 Participants |
| Cohort 2 | Observed Rate of STRONG POSITIVE Anti-SARS-CoV2 Antibody Response | 23 Participants |
| Cohort 3 | Observed Rate of STRONG POSITIVE Anti-SARS-CoV2 Antibody Response | 15 Participants |