Donor-Derived Humoral Immunity, Hematopoietic Stem Cell Transplantation, TAR
Study Details
Study Description
Brief Summary
This research study is for subjects that are receiving a bone marrow transplant. As part of the transplant subjects will receive stem cells from a donor who has agreed to donate stem cells for them. Unfortunately, it takes a long time for the immune system to recover after a bone marrow transplant. This makes it more likely for patients to develop serious infections.
This study is being done to better understand how the immune system will recover after transplant. The immune system includes the cells that help fight infection. This study will help investigators understand which patients are at risk for developing infections after transplant.
All children and adults receive standard vaccines (shots) during their lifetime to provide protection from many different infections. One such infection is tetanus, a bacteria that can cause life-threatening problems. After transplant patients no longer have protection from infections such as tetanus. Therefore, most patients need to receive all their vaccine (shots) again after transplant. This is usually done 1-2 years after transplant, since it may take that long for patients to have a normal immune system.
However, the investigators believe that the time it will take for the patient to develop normal protection against tetanus can be shortened if both the patient and the patient's stem cell donor receive a tetanus vaccine.
The goal of this study is to determine if giving a tetanus vaccine to the donor and the patient will provide the patient with enough protection (immunity) to prevent infection following bone marrow transplant.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
To participate in this study, patients will need to have given informed consent to have a bone marrow transplant. Before receiving the tetanus vaccine, we would like to test the patient's immune system against tetanus. We will again want to test the patient's immune system against tetanus on the day the patient receives the bone marrow transplant. Approximately 3 months after transplant, if the patient is still eligible, they will receive an additional tetanus booster shot. We will again draw blood to test their immune system against tetanus at the time points listed below.
TREATMENT PLAN:
If the subject meets eligibility requirements and consents to be part of this study, we will collect 8 mL (1.7 teaspoons) of blood from the subject to test their immunity 7 to 10 days before their bone marrow transplant. The subject will receive a tetanus vaccine (given as an injection into the upper arm or thigh muscle) on that same day. We will then collect approximately the same amount of blood (2 teaspoons) on the day the patient would receive the bone marrow transplant. We will also collect the same amount of blood 1 week, 2 weeks, 4 weeks and 3 months, 6 months and 12 months after the transplant. This will help us to see how the patients immune system responded to the vaccine.
Three months after the transplant, the patient will receive an additional tetanus vaccine (known as a booster shot), but only if the patient is still eligible to receive it. Patient's will only be eligible to receive the booster shot if they remain well and do not have any other problems such as severe infection, graft versus host disease or relapse. We will collect 8 ml (1.7 teaspoons) of blood 1 week, 2 weeks and 4 weeks after receiving the booster shot to determine if they respond to the vaccine.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single arm: Tetanus Toxoid SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest |
Biological: Tetanus
Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest.
Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose).
Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Antibody Recall Response Rate [4 months]
The proportion of participants with antibody recall response along with 95% confidence intervals will be calculated.
Secondary Outcome Measures
- Change in Immunoglobulin Levels [up to 12 months]
Changes from baseline to several time points during follow-up will be calculated.
Eligibility Criteria
Criteria
INCLUSION CRITERIA:
Inclusion Criteria for Donors:
-
Related donor of bone marrow or peripheral blood stem cell product
-
Age 3 to 70 years
-
Informed consent form signed and sent to Research Coordinator
Inclusion Criteria for Recipients:
-
Patient with acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, myeloproliferative disorder, Hodgkin lymphoma, non-Hodgkin lymphoma, or a non-malignant disease requiring allogeneic stem cell transplant
-
Age between 3 and 70 years
-
Informed consent form signed and sent to Research Coordinator
EXCLUSION CRITERIA:
Exclusion Criteria for Donors:
-
Allergy to tetanus vaccine
-
Pregnant or lactating
-
Has received tetanus booster within preceding 12 months
Exclusion Criteria for Recipients to Receive FIRST Tetanus Immunization:
-
Allergy to tetanus vaccine
-
Has received tetanus booster within preceding 12 months
-
Has active malignancy (not in remission)
Exclusion Criteria for Recipients to Receive SUBSEQUENT Tetanus Immunization:
-
Allergy to tetanus vaccine
-
Active, acute graft vs. host disease (GVHD) greater than or equal to grade II or chronic graft vs. host disease (GVHD)
-
Disease relapse - less than 75% donor chimerism (peripheral blood or bone marrow)
-
Active infection (bacterial, viral, fungal) or fever (temperature greater than 100.5 celsius)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Texas Childen's Hospital | Houston | Texas | United States | 77030 |
| 2 | The Methodist Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Robert Krance
- Baylor College of Medicine
- The Methodist Hospital Research Institute
- Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
- Study Director: Robert Krance, MD, Texas Childrens Hospital / Baylor College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- H-21942-TAR
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Single Arm: Tetanus Toxoid |
|---|---|
| Arm/Group Description | SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest Tetanus: Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest. Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose). Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection. |
| Period Title: Overall Study | |
| STARTED | 7 |
| COMPLETED | 5 |
| NOT COMPLETED | 2 |
Baseline Characteristics
| Arm/Group Title | Single Arm: Tetanus Toxoid |
|---|---|
| Arm/Group Description | SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest Tetanus: Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest. Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose). Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection. |
| Overall Participants | 7 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
7
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
28.6%
|
| Male |
5
71.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
5
71.4%
|
| Not Hispanic or Latino |
2
28.6%
|
| Unknown or Not Reported |
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Black |
1
14.3%
|
| White |
6
85.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
7
100%
|
Outcome Measures
| Title | Antibody Recall Response Rate |
|---|---|
| Description | The proportion of participants with antibody recall response along with 95% confidence intervals will be calculated. |
| Time Frame | 4 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant was off study on day 68 and not included in this analysis. |
| Arm/Group Title | Single Arm: Tetanus Toxoid |
|---|---|
| Arm/Group Description | SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest Tetanus: Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest. Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose). Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection. |
| Measure Participants | 6 |
| Number (95% Confidence Interval) [proportion of participants] |
0.167
2.4%
|
| Title | Change in Immunoglobulin Levels |
|---|---|
| Description | Changes from baseline to several time points during follow-up will be calculated. |
| Time Frame | up to 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| One participant was off study on day 68 and not included in this analysis. Six participants included in the analysis had at least one measurement at the follow-up time points. n=the number of participants with measurements for that time point. |
| Arm/Group Title | Single Arm: Tetanus Toxoid |
|---|---|
| Arm/Group Description | SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest Tetanus: Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest. Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose). Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection. |
| Measure Participants | 6 |
| IgA Change at 3 months |
-49.9
|
| IgA Change at 6 months |
-1.0
|
| IgA Change at 12 months |
7.7
|
| IgG Change at 3 months |
-677.6
|
| IgG Change at 6 months |
-668.2
|
| IgG Change at 12 months |
-683.0
|
| IgM Change at 3 months |
13.7
|
| IgM Change at 6 months |
45.0
|
| IgM Change at 12 months |
75.8
|
Adverse Events
| Time Frame | Toxicities will be assessed while patients are receiving tetanus toxoid and for 6 weeks following last vaccination, either 6 weeks after the first booster or 6 weeks after the second booster, if the patient receives the second booster. | |
|---|---|---|
| Adverse Event Reporting Description | All adverse events were collected using CTCAE 3.0 for the study. For reporting purpose, adverse event terms were converted using CTCAE v4.0. | |
| Arm/Group Title | Single Arm: Tetanus Toxoid | |
| Arm/Group Description | SCT Donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest Tetanus: Stem cell transplant donors will receive one dose of tetanus toxoid 0.5mL intramuscularly into deltoid or medial lateral thigh 7-10 days prior to bone marrow or peripheral blood stem cell harvest. Stem cell transplant recipients will receive one dose of tetanus toxoid 0.5mL intramuscularly (or subcutaneously if platelet count less than 50,000/uL) into deltoid or medial lateral thigh 7-10 days prior to stem cell transplant (FIRST dose). Stem cell transplant recipients will receive a subsequent dose of tetanus toxoid 0.5mL given intramuscularly into deltoid or medial lateral thigh (or given subcutaneously if platelet count is less than 50,000/uL) approximately 3 months following allo stem cell transplant. Patients must meet re-evaluation criteria to receive injection. | |
All Cause Mortality |
||
| Single Arm: Tetanus Toxoid | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | |
Serious Adverse Events |
||
| Single Arm: Tetanus Toxoid | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/7 (28.6%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||
| Diarrhea | 1/7 (14.3%) | 1 |
| Vomiting | 1/7 (14.3%) | 1 |
| Infections and infestations | ||
| Infection - Other: Gastrointestinal Abdomen | 1/7 (14.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Single Arm: Tetanus Toxoid | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | |
| Blood and lymphatic system disorders | ||
| Febrile neutropenia(fever of unknown origin wo clinically or microbiologically documented infection) | 2/7 (28.6%) | 2 |
| Cardiac disorders | ||
| Supraventricular and nodal arrhythmia - Sinus arrhythmia | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||
| Constipation | 1/7 (14.3%) | 1 |
| Diarrhea | 3/7 (42.9%) | 7 |
| Mucositis/stomatitis (clinical exam) - Oral cavity | 1/7 (14.3%) | 4 |
| Nausea | 4/7 (57.1%) | 10 |
| Pain - Abdomen NOS | 2/7 (28.6%) | 4 |
| Pain - Other: Oral Cavity | 1/7 (14.3%) | 1 |
| Vomiting | 4/7 (57.1%) | 14 |
| General disorders | ||
| Fatigue (asthenia, lethargy, malaise) | 1/7 (14.3%) | 1 |
| Fatigue (lethargy, malaise, asthenia) | 1/7 (14.3%) | 1 |
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | 3/7 (42.9%) | 5 |
| Pain - Pain NOS | 1/7 (14.3%) | 1 |
| Rigors/chills | 2/7 (28.6%) | 2 |
| Immune system disorders | ||
| Allergic reaction/hypersensitivity (including drug fever) | 3/7 (42.9%) | 3 |
| Infections and infestations | ||
| Mucosal infection | 1/7 (14.3%) | 1 |
| Infection(documented clinically or microbiologically) with Grade 3 or 4 neutrophils-Bladder(urinary) | 1/7 (14.3%) | 1 |
| Infection - Other: Mucosa | 1/7 (14.3%) | 3 |
| Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS | 1/7 (14.3%) | 1 |
| Pulmonary/Upper Respiratory - Other: Rhinorrhea | 1/7 (14.3%) | 2 |
| Investigations | ||
| ALT, SGPT (serum glutamic pyruvic transaminase) | 3/7 (42.9%) | 11 |
| AST, SGOT(serum glutamic oxaloacetic transaminase) | 6/7 (85.7%) | 22 |
| Bilirubin (hyperbilirubinemia) | 2/7 (28.6%) | 2 |
| GGT (gamma-Glutamyl transpeptidase) | 3/7 (42.9%) | 8 |
| Lipase | 1/7 (14.3%) | 1 |
| PTT (Partial Thromboplastin Time) | 1/7 (14.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Albumin, serum-low (hypoalbuminemia) | 7/7 (100%) | 21 |
| Bicarbonate, serum-low | 4/7 (57.1%) | 11 |
| Calcium, serum-high (hypercalcemia) | 2/7 (28.6%) | 2 |
| Calcium, serum-low (hypocalcemia) | 5/7 (71.4%) | 22 |
| Glucose, serum-high (hyperglycemia) | 2/7 (28.6%) | 7 |
| Glucose, serum-low (hypoglycemia) | 1/7 (14.3%) | 3 |
| Magnesium, serum-low (hypomagnesemia) | 5/7 (71.4%) | 21 |
| Phosphate, serum-low (hypophosphatemia) | 2/7 (28.6%) | 2 |
| Potassium, serum-high (hyperkalemia) | 3/7 (42.9%) | 4 |
| Potassium, serum-low (hypokalemia) | 3/7 (42.9%) | 8 |
| Sodium, serum-low (hyponatremia) | 7/7 (100%) | 15 |
| Triglyceride, serum-high (hypertriglyceridemia) | 2/7 (28.6%) | 2 |
| Musculoskeletal and connective tissue disorders | ||
| Pain - Back | 1/7 (14.3%) | 2 |
| Pain - Bone | 2/7 (28.6%) | 2 |
| Pain - Extremity-limb | 2/7 (28.6%) | 2 |
| Pain - Joint | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||
| Pain - Head/headache | 1/7 (14.3%) | 1 |
| Pain - Other: Headache | 1/7 (14.3%) | 3 |
| Tremor | 1/7 (14.3%) | 1 |
| Psychiatric disorders | ||
| Personality/behavioral | 1/7 (14.3%) | 1 |
| Renal and urinary disorders | ||
| Hemorrhage, GU - Urinary NOS | 1/7 (14.3%) | 2 |
| Pain - Bladder | 2/7 (28.6%) | 2 |
| Proteinuria | 1/7 (14.3%) | 2 |
| Reproductive system and breast disorders | ||
| Pain - Vagina | 1/7 (14.3%) | 1 |
| Sexual/Reproductive Function - Other: Menstrual cramps | 1/7 (14.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 3/7 (42.9%) | 4 |
| Dyspnea (shortness of breath) | 1/7 (14.3%) | 1 |
| Epistaxis | 3/7 (42.9%) | 3 |
| Pulmonary/Upper Respiratory - Other: Wheezing | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Bruising (in absence of Grade 3 or 4 thrombocytopenia) | 1/7 (14.3%) | 1 |
| Dry skin | 1/7 (14.3%) | 1 |
| Rash/desquamation | 4/7 (57.1%) | 6 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Robert A. Krance |
|---|---|
| Organization | Baylor College of Medicine |
| Phone | 832-824-4661 |
| rakrance@txch.org |
- H-21942-TAR