Accelerated Phase CML, BCR-ABL1 Positive, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission, Chronic Lymphocytic Leukemia, Chronic Phase CML, BCR-ABL1 Positive, Cytomegalovirus Positive, Donor, Hematopoietic Cell Transplant Recipient, Hodgkin Lymphoma, Myelodysplastic Syndrome, Myelodysplastic/Myeloproliferative Neoplasm, Non-Hodgkin Lymphoma, Myelofibrosis, Hematopoietic and Lymphoid Cell Neoplasm
Conditions
Brief summary
This phase II trial studies how well multi-peptide CMV-modified vaccinia Ankara (CMV-MVA Triplex) vaccination of stem cell donors works in preventing cytomegalovirus (CMV) viremia in participants with blood cancer undergoing donor stem cell transplant. Giving a vaccine to the donors may boost the recipient's immunity to this virus and reduce the chance of CMV disease after transplant.
Detailed description
PRIMARY OBJECTIVES: I. Establish the feasibility and safety of priming CMV immunity in donors by Triplex vaccination prior to peripheral blood stem cell (PBSC) harvest. SECONDARY OBJECTIVES: I. Examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events. OUTLINE: Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. Participants undergo hematopoietic cell transplantation on day 0. After completion of study treatment, participants are followed up for 1 year.
Interventions
Given via injection
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* DONOR: Ability to comprehend the investigational nature of the study and provide informed consent * DONOR: Willing to receive Triplex vaccination, a minimum of 14 days prior to the PBSC collection * DONOR VACCINATION: Donors are eligible to be vaccinated prior to the determination of their human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV) status. The
Exclusion criteria
for transplant is independent of eligibility for vaccination and is determined by the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delayed Engraftment | Up to 1 year from stem cell infusion. | Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 109/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery. |
| Severe (Grade III-IV) Acute Graft Versus Host Disease | Up to 6 months from stem cell infusion | Acute graft versus host disease (aGvHD) happens within days or as late as 6 months after allogeneic transplants. The three main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract. |
| Number of Recipients With Grade 3-4 Adverse Events | Up to 1 year from stem cell infusion. | Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0. |
| Number of Donors With Grade 2-3 Adverse Events | Up to 6 months after G-CSF mobilization | Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0. |
| 100-Day Non-Relapse Mortality (NRM) | From stem cell infusion up to 100 days post-HSCT (hematopoietic stem cell transplantation). | NRM was defined as death without recurrent or progressive disease after allogeneic transplant. Probabilities of NRM were estimated with the use of cumulative incidence curves, with relapse viewed as a competing risk. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donor (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) Donors receive multi-peptide CMV-modified vaccinia Ankara vaccine injection between days -60 and -10 prior to granulocyte colony stimulating factor mobilization. | 17 |
| Receipient (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) Participants undergo hematopoietic cell transplantation on day 0 and receive multi-peptide CMV-modified Vaccinia Ankara vaccine injection on days 28 and 56. | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | Donor (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | Total | Receipient (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) |
|---|---|---|---|
| Age, Continuous | 53 years | 53 years | 56 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 16 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 11 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 23 Participants | 12 Participants |
| Region of Enrollment United States | 17 participants | 34 participants | 17 participants |
| Sex: Female, Male Female | 10 Participants | 19 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 2 / 17 |
| other Total, other adverse events | 16 / 17 | 5 / 17 |
| serious Total, serious adverse events | 0 / 17 | 2 / 17 |
Outcome results
Primary
100-Day Non-Relapse Mortality (NRM)
NRM was defined as death without recurrent or progressive disease after allogeneic transplant. Probabilities of NRM were estimated with the use of cumulative incidence curves, with relapse viewed as a competing risk.
Time frame: From stem cell infusion up to 100 days post-HSCT (hematopoietic stem cell transplantation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Recipients (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | 100-Day Non-Relapse Mortality (NRM) | 0 percentage of evaluable participants |
Primary
Delayed Engraftment
Time to neutrophil engraftment was defined as days from stem cell infusion to the first of three consecutive days of absolute neutrophil count ≥0.5 x 109/L. Delayed engraftment was defined as ≥20 days to neutrophil recovery.
Time frame: Up to 1 year from stem cell infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | Delayed Engraftment | 0 Participants |
Primary
Number of Donors With Grade 2-3 Adverse Events
Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
Time frame: Up to 6 months after G-CSF mobilization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | Number of Donors With Grade 2-3 Adverse Events | 3 Participants |
Primary
Number of Recipients With Grade 3-4 Adverse Events
Toxicities were assessed in recipients by Common Terminology Criteria for Adverse Events version 4.0.
Time frame: Up to 1 year from stem cell infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | Number of Recipients With Grade 3-4 Adverse Events | 0 Participants |
Primary
Severe (Grade III-IV) Acute Graft Versus Host Disease
Acute graft versus host disease (aGvHD) happens within days or as late as 6 months after allogeneic transplants. The three main tissues that acute GVHD affects are the skin, liver, and gastrointestinal tract.
Time frame: Up to 6 months from stem cell infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients (Multi-peptide CMV-modified Vaccinia Ankara Vaccine) | Severe (Grade III-IV) Acute Graft Versus Host Disease | 2 Participants |