Heart TransplantNCT02182986
Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children
An observational study of Heart Transplant and Small Intestine Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
Trial summary
Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a… Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Heart Transplant, Small Intestine Transplant, Kidney Transplant
- What is being tested?
- transplant and Immunosuppressive Drugs
- Type of treatment
- Surgery or procedure
- How many people
- 944 participants
- Where
- 7 sitesUnited States
- Study dates
- 14 Aug 2014to 15 May 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Pediatric Candidates for or recipients of heart, liver, heart with liver, kidney, small intestine, or liver with small intestine at participating major pediatric solid organ transplant programs
Who may be able to join
- Subject and/or parent or legal guardian must be able to understand and provide informed consent/assent;
- Candidate for or recipient of: heart, liver, heart with liver, small intestine, liver with small intestine, or kidney; and
- Subject enrolled within 3 years of transplant.
Who cannot join
- Previous diagnosis of PTLD;
- Transplant recipients of lung alone, or in combination with an eligible organ type;
- Pancreas transplantation with the exception of 'en bloc' transplant in combined liver and small intestine multivisceral transplantation;
- Any combination other than listed in inclusion criteria;
- History of any previous solid organ, stem cell, or bone marrow transplantation;
- Inability or unwillingness of the legal guardian and/or the subject to comply with the study protocol.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University of Texas Southwestern
Dallas, Texas, 75235
University of California, Los Angeles
Los Angeles, California, 90095
University of Miami Health System
Miami, Florida, 33101
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Lucile Packard Children's Hospital Stanford
Stanford, California, 94305
Medstar Georgetown Transplant Institute
Washington D.C., District of Columbia, 20057
About this study
Official title: Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children (CTOTC-06)
Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a very serious cancer that is linked to Epstein-Barr virus (EBV).
Read the detailed description
EBV-associated post-transplant lymphoproliferative disease (PTLD) is the most common malignancy in children after transplant. Diagnosis and effective treatment of the EBV-associated cancer is hampered by our inability to determine which children are at risk of developing these cancers and to detect the cancer at an early stage. In this study, we plan to test new "biomarkers" in the blood of children that will tell us very early on if the child is at risk of developing the EBV-associated cancer or if the cancer is present. These studies provide new opportunities for detection, diagnosis, and treatment of children with EBV-associated, post-transplant cancer.
- Conditions
- Heart Transplant, Small Intestine Transplant, Kidney Transplant, Liver Transplant, EBV-Related PTLD, PTLDs
- Being tested
- transplant, Immunosuppressive Drugs
- Keywords
- Biomarkers, Post-Transplant Lymphoproliferative Disorders (PTLDs)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transplantProcedure or surgery
Also called transplantation
All subjects enrolled in this study are candidates for/recipients of solid organ transplants as a therapeutic for end stage diseases (e.g., heart, liver, heart with liver, kidney, small intestine, or liver with small intestine transplants).
Immunosuppressive DrugsDrug
Also called Immunosuppressive Medications
Immunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft.
| Study group | Role | What they receive |
|---|---|---|
| Subjects Enrolled Pre-Transplant | Subjects (N=approximately 357) Enrolled Pre-Transplant
* Subjects with evidence of EBV infection prior to transplant
* Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant Receives: Procedure: transplant; Drug: Immunosuppressive Drugs | |
| Subjects Enrolled Post-Transplant | Subjects (N=approximately 588) Enrolled 3 Yrs Post-Transplant
* Subjects with evidence of EBV infection prior to transplant
* Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant Receives: Procedure: transplant; Drug: Immunosuppressive Drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD)
The development of EBV positive PTLD during the study period as assessed by the local site pathologist, with confirmation of the PTLD diagnosis by the Study Clinicopathological Review Board (SCPRB)
Measured: Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment
Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1)
Specified gain-of-function mutations in EBV LMP-1 (e.g., corresponding to EBV LMP-1 variants G212S or S366T) detected by polymerase chain reaction (PCR) method
Measured: Receipt of transplanted organ(s) to confirmation of mutations in EBV LMP1 , up to year 4 post - enrollment
Pathogenic Changes in B Cell Clonotype Development
Pathogenic changes in B cell clonotype development as assessed using high throughput sequencing (HTS)
Measured: Receipt of transplanted organ(s) to confirmation of changes in B cell clonotype development, up to year 4 post - enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2014 (estimated)
- Study start14 Aug 2014
- Primary completion15 May 2019
- Study completion15 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 944 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Clinical Trials in Organ Transplantation in Children
- Responsible party
- Sponsor
- Investigators
- Carlos Esquivel, M.D., Ph.D., Principal investigator, Stanford UniversityDaniel Bernstein, M.D., Study chair, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02182986
- Sponsor's protocol ID
- DAIT CTOTC-06
- Status last verified
- Aug 2019
- First submitted
- 30 Jun 2014
- Last updated
- 29 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Tajima T, Martinez OM, Bernstein D, Boyd SD, Gratzinger D, Lum G, Sasaki K, Tan B, Twist CJ, Weinberg K, Armstrong B, Desai DM, Mazariegos GV, Chin C, Fishbein TM, Tekin A, Venick RS, Krams SM, Esquivel CO. Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States. Pediatr Transplant. 2024 Jun;28(4):e14763. doi: 10.1111/petr.14763.
PubMed 38682750Rao M, Amouzgar M, Harden JT, Lapasaran MG, Trickey A, Armstrong B, Odim J, Debnam T, Esquivel CO, Bendall SC, Martinez OM, Krams SM. High-dimensional profiling of pediatric immune responses to solid organ transplantation. Cell Rep Med. 2023 Aug 15;4(8):101147. doi: 10.1016/j.xcrm.2023.101147. Epub 2023 Aug 7.
PubMed 37552988
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers for Post-Transplant Lymphoproliferative Disorders in Children (CTOTC-06)
- ClinicalTrials.gov ID
- NCT02182986
- Acronym / sponsor ID
- DAIT CTOTC-06
- Conditions
- Heart Transplant, Small Intestine Transplant, Kidney Transplant, Liver Transplant, EBV-Related PTLD, PTLDs
- Keywords
- Biomarkers, Post-Transplant Lymphoproliferative Disorders (PTLDs)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 944 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Clinical Trials in Organ Transplantation in Children
- Study start
- 14 Aug 2014 (actual)
- Primary completion
- 15 May 2019 (actual)
- Study completion
- 15 May 2019 (actual)
- First posted
- 8 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Solid organ transplantation is an important therapeutic option for children with a variety of end stage diseases. However, the same immunosuppressive medications that are required to prevent the child's immune system from attacking and rejecting the transplanted organ can predispose these individuals to developing a very serious cancer that is linked to Epstein-Barr virus (EBV).
Detailed description
EBV-associated post-transplant lymphoproliferative disease (PTLD) is the most common malignancy in children after transplant. Diagnosis and effective treatment of the EBV-associated cancer is hampered by our inability to determine which children are at risk of developing these cancers and to detect the cancer at an early stage. In this study, we plan to test new "biomarkers" in the blood of children that will tell us very early on if the child is at risk of developing the EBV-associated cancer or if the cancer is present. These studies provide new opportunities for detection, diagnosis, and treatment of children with EBV-associated, post-transplant cancer.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects Enrolled Pre-Transplant | – | Procedure: transplant, Drug: Immunosuppressive DrugsSubjects (N=approximately 357) Enrolled Pre-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant |
| Subjects Enrolled Post-Transplant | – | Procedure: transplant, Drug: Immunosuppressive DrugsSubjects (N=approximately 588) Enrolled 3 Yrs Post-Transplant * Subjects with evidence of EBV infection prior to transplant * Subjects without evidence of EBV infection prior to transplant, who are at risk of developing EBV infection after transplant |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Pediatric Candidates for or recipients of heart, liver, heart with liver, kidney, small intestine, or liver with small intestine at participating major pediatric solid organ transplant programs
Key inclusion criteria (3 listed)
- Subject and/or parent or legal guardian must be able to understand and provide informed consent/assent;
- Candidate for or recipient of: heart, liver, heart with liver, small intestine, liver with small intestine, or kidney; and
- Subject enrolled within 3 years of transplant.
Key exclusion criteria (6 listed)
- Previous diagnosis of PTLD;
- Transplant recipients of lung alone, or in combination with an eligible organ type;
- Pancreas transplantation with the exception of 'en bloc' transplant in combined liver and small intestine multivisceral transplantation;
- Any combination other than listed in inclusion criteria;
- History of any previous solid organ, stem cell, or bone marrow transplantation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| transplantAlso: transplantationAll subjects enrolled in this study are candidates for/recipients of solid organ transplants as a therapeutic for end stage diseases (e.g., heart, liver, heart with liver, kidney, small intestine, or liver with small intestine transplants). | Procedure or surgery | Subjects Enrolled Post-Transplant, Subjects Enrolled Pre-Transplant |
| Immunosuppressive DrugsAlso: Immunosuppressive MedicationsImmunosuppressive drugs prescribed as standard of care to prevent rejection of the allograft. | Drug | Subjects Enrolled Post-Transplant, Subjects Enrolled Pre-Transplant |
Primary outcome
Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD)
Time frame: Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment
The development of EBV positive PTLD during the study period as assessed by the local site pathologist, with confirmation of the PTLD diagnosis by the Study Clinicopathological Review Board (SCPRB)
Specified Gain-of-Function Mutations in EBV Latent Membrane Protein 1 (LMP-1)
Time frame: Receipt of transplanted organ(s) to confirmation of mutations in EBV LMP1 , up to year 4 post - enrollment
Specified gain-of-function mutations in EBV LMP-1 (e.g., corresponding to EBV LMP-1 variants G212S or S366T) detected by polymerase chain reaction (PCR) method
Pathogenic Changes in B Cell Clonotype Development
Time frame: Receipt of transplanted organ(s) to confirmation of changes in B cell clonotype development, up to year 4 post - enrollment
Pathogenic changes in B cell clonotype development as assessed using high throughput sequencing (HTS)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2019.
- Derived from this study: PubMed 38682750Tajima T, Martinez OM, Bernstein D, Boyd SD, Gratzinger D, Lum G, Sasaki K, Tan B, Twist CJ, Weinberg K, Armstrong B, Desai DM, Mazariegos GV, Chin C, Fishbein TM, Tekin A, Venick RS, Krams SM, Esquivel CO. Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States. Pediatr Transplant. 2024 Jun;28(4):e14763. doi: 10.1111/petr.14763.
- Derived from this study: PubMed 37552988Rao M, Amouzgar M, Harden JT, Lapasaran MG, Trickey A, Armstrong B, Odim J, Debnam T, Esquivel CO, Bendall SC, Martinez OM, Krams SM. High-dimensional profiling of pediatric immune responses to solid organ transplantation. Cell Rep Med. 2023 Aug 15;4(8):101147. doi: 10.1016/j.xcrm.2023.101147. Epub 2023 Aug 7.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Clinical Trials in Organ Transplantation in Children (CTOT-C)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carlos Esquivel, M.D., Ph.D. principal investigator
Stanford University
Daniel Bernstein, M.D. study chair
Stanford University
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Transplant and Small Intestine Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Epstein-Barr Virus (EBV) Positive Post-Transplant Lymphoproliferative Disorders (PTLD) (time frame: Receipt of transplanted organ(s) to confirmation of EBV-positive PTLD, up to year 4 post - enrollment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02182986, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2019.