Chronic Lymphocytic Leukemia (CLL), Waldenstrom Macroglobulinemia (WM)
Conditions
Keywords
shingles vaccine (Shingrix), Chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM), Pilot Study
Brief summary
The primary objective of the study is to assess the capability of a patient with Chronic Lymphocytic Leukemia (CLL) or Waldenström Macroglobulinemia (WM) to generate an immune response to the Shingrix vaccine under first-line BTK inhibitors.
Detailed description
Chronic lymphocytic leukemia (CLL) and Waldenstrom's macroglobulinemia (WM) are known risk factors for zoster reactivation, commonly called shingles. Although a recently FDA-approved recombinant, adjuvanted herpes zoster vaccine (Shingrix) is currently being offered to these populations, no study has specifically evaluated them. The purpose of the study is to complete a single-arm trial evaluating if patients with CLL or WM, while on treatment with first-line BTK inhibitors, can achieve immunologic response to Shingrix. If effective, this will result in a new, well-tolerated shingles prevention strategy for these patients. The primary objective is to assess the capability to mount a humoral immune response to Shingrix in patients with CLL or WM under first-line BTK inhibitors.
Interventions
DRUGShingrix vaccine
On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose.
Sponsors
GlaxoSmithKline
University of Rochester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* They are at least 50 years of age; * Have been diagnosed with chronic lymphocytic leukemia (CLL) OR Waldenström's macroglobulinemia (WM) * Have been on first-line BTK inhibitor (ie ibrutinib or acalabrutinib) for at least 3 months, * Prior treatment with single agent rituximab is permitted if last dose was administered over one year ago; * Have at least a one-year life expectancy; * Have a history of varicella (chicken-pox) OR lived in the US or any endemic country for \> 30 years. * Prior radiation therapy is allowed
Exclusion criteria
* They have a known hypersensitivity to a vaccine component; * Had herpes zoster reactivation within the past year; * Had received or were scheduled to receive a live virus vaccine in the period from 4 weeks prior to Dose 1 through 28 days post-second dose; * Had received or were scheduled to receive an inactivated vaccine in the period ranging from 7 days prior to Dose 1 through 7 days post- second dose; * Are unable to give informed consent; * Have absolute lymphocyte counts greater than 20,000 X 109/L; * Are receiving treatment for CLL or WM with an additional agent other than a BTK inhibitor; * Had rituximab treatment within a year prior to study start; * Had prior chemotherapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration | 4 weeks following the second vaccination, at approximately 3 months | Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cellular Response to Vaccination 4 Weeks After the Second Vaccine Administration | 4 weeks following the second vaccination, at approximately 3 months | Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 4 weeks after the second vaccine administration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Humoral Response to Vaccination 2 Years After the Second Vaccine Administration | 2 years following second vaccination, approximately 26 months from day 1 | Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects |
| Number of Participants With Cellular Response to Vaccination 2 Years After the Second Vaccine Administration | 2 years following second vaccination, approximately 26 months from day 1 | Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 2 years after the second vaccine administration. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Shingrix Vaccine On day one, patients will receive the first of two doses of the Shingrix vaccine administered as an injection into the muscle in their upper arm. The second dose of vaccine will be administered as an injection to their upper arm approximately 2 months after the first dose. Antibody and cellular response to vaccination will be assessed at 4 weeks and 24 months after the second dose. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Shingrix Vaccine |
|---|---|
| Age, Customized 50 to 65 years | 12 Participants |
| Age, Customized > 65 years | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 0 / 32 |
| serious Total, serious adverse events | 1 / 32 |
Outcome results
Primary
Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration
Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects
Time frame: 4 weeks following the second vaccination, at approximately 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shingrix Vaccine | Number of Participants With Humoral Response to Vaccination 4 Weeks After the Second Vaccine Administration | 24 Participants |
Secondary
Number of Participants With Cellular Response to Vaccination 4 Weeks After the Second Vaccine Administration
Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 4 weeks after the second vaccine administration.
Time frame: 4 weeks following the second vaccination, at approximately 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shingrix Vaccine | Number of Participants With Cellular Response to Vaccination 4 Weeks After the Second Vaccine Administration | 26 Participants |
Other Pre-specified
Number of Participants With Cellular Response to Vaccination 2 Years After the Second Vaccine Administration
Cellular response, as determined by measuring VZgE-specific T-cell responses in blood, 2 years after the second vaccine administration.
Time frame: 2 years following second vaccination, approximately 26 months from day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shingrix Vaccine | Number of Participants With Cellular Response to Vaccination 2 Years After the Second Vaccine Administration | 17 Participants |
Other Pre-specified
Number of Participants With Humoral Response to Vaccination 2 Years After the Second Vaccine Administration
Vaccine response, as determined by blood antibody levels to the varicella virus glycoprotein E subunit (anti-gE); Baseline is defined as pre-vaccination anti-gE titer in seropositive subjects, and the lower limit of detection in seronegative subjects
Time frame: 2 years following second vaccination, approximately 26 months from day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Shingrix Vaccine | Number of Participants With Humoral Response to Vaccination 2 Years After the Second Vaccine Administration | 13 Participants |