Graft Versus Host DiseaseNCT02109809
Low-Dose Total Lymphoid Irradiation in Treating Patients With Refractory Chronic Graft-versus-Host Disease After Donor Stem Cell Transplant
A study testing total nodal irradiation, laboratory biomarker analysis and questionnaire administration in people with Graft Versus Host Disease, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of low-dose total lymphoid irradiation (LD-TLI) in treating patients with chronic graft-versus-host disease that has not responded to treatment with steroids. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Versus Host Disease
- What is being tested?
- total nodal irradiation, laboratory biomarker analysis and questionnaire administration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Sep 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients may have received a prior allogeneic hematopoietic stem cell transplant (alloHSCT) for any indication and from any donor
- Patients must have a diagnosis of cGvHD, in accordance with National Institutes of Health (NIH) guidelines; patients with "overlap syndrome" are also eligible; NOTE: Patients with recurrent, late onset and/or persistent acute GvHD (alone) are not eligible
- Patients with chronic GvHD who have been exposed to two or more lines of therapy, including at least one of which was composed of a glucocorticoid and a calcineurin inhibitor are eligible.
- Patients must have active, but not rapidly progressive, refractory cGvHD; any degree of severity (as per NIH criteria) and/or pattern of organ involvement may be considered; that said, patients with more severe and/or extensive chronic GvHD are expected to be the usual candidates for therapy
- As above, GvHD should be controlled to a degree that would potentially allow no additional requirement for systemic IST before and following TLI =< -15 and >= day (d) +45, respectively
- The ability to administer protocol doses of TLI (i.e., 100, 200 or 300 cGy) without exceeding cumulative doses of radiation must be established; for patients with prior radiotherapy exposure, this determination will be made by Dr. Greven (or her designee) using published guidelines for excessive organ exposure
Show all 18Show fewer
- Karnofsky performance status (KPS) >= 60%
- White blood cells >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Hemoglobin >= 10.0 g/dL
- Platelets >= 100,000/mcL
- NOTE: If such hematologic abnormalities are present and deemed due to the process of cGvHD, such requirements may be waived with the approval of the PI
- Patients must have non-hematologic organ function as defined below:
- Left ventricular ejection fraction (LVEF) > 40%
- Key pulmonary function tests (PFTs) > 40%
- No further criteria for non-hematologic organ function are specified; however, if moderate-to-severe (major) organ function is present, such should be discussed with the PI, as various degrees of non-hematologic organ dysfunction may compromise either (or both) outcomes and toxicity evaluation
- If there is concern regarding potential reversibility of any specific organ dysfunction, this issue should be addressed by consultation with an appropriate sub-specialist
- Ability to understand and the willingness to sign an institutional review board (IRB)-approved informed consent document
Who cannot join
- Patients with evidence of persistent or active malignancy or uncontrolled infection at the time of study entry
- Patients who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I Study: Low-Dose Total Lymphoid Irradiation in the Treatment of Refractory Chronic Graft Versus Host Disease
This phase I trial studies the side effects and best dose of low-dose total lymphoid irradiation (LD-TLI) in treating patients with chronic graft-versus-host disease that has not responded to treatment with steroids. LD-TLI is a procedure in which all of the body's major lymph nodes are treated with small doses of radiation in order to reset the dysfunctional immune system. LD-TLI may work as a treatment for graft-versus-host disease caused by a bone marrow or stem cell transplant.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the safety of total lymphoid irradiation (TLI) in cohorts of a selected population of refractory chronic graft-versus-host disease (GvHD) patients, given to cohorts with a total cumulative doses of TLI of 100, 150, 200, 250 or 300 centigray (cGy).
SECONDARY OBJECTIVES:
- To evaluate the efficacy (failure free survival [FFS] at 6 months) of this therapy in the study population.
II. Approximate the efficacy at different dose levels using the GvHD summary scores.
TERTIARY OBJECTIVES:
- Determine the effect of this therapy on relevant subpopulations of immune cells in an attempt to elucidate a mechanism of action.
OUTLINE: This is a dose-escalation study.
Patients undergo LD-TLI daily for 1-2 days.
After completion of study treatment, patients are followed up on day 45, at 3 and 6 months, at 1 year, and then every 6 months thereafter.
- Conditions
- Graft Versus Host Disease
- Being tested
- total nodal irradiation, laboratory biomarker analysis, questionnaire administration
- Medical subject headings
- Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
total nodal irradiationRadiation
Also called TLI, total lymphoid irradiation
Undergo TLI
laboratory biomarker analysisOther
Correlative studies
questionnaire administrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Supportive Care (TLI) | Experimental | Patients undergo LD-TLI daily for 1-2 days. Receives: Radiation: total nodal irradiation; Other: laboratory biomarker analysis; Other: questionnaire administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0
Toxicities (grade 2 and higher) will be reported as number of occurrences.
Measured: At day 180
Failure Free Survival (FFS) as Assessed by Scoring for Chronic GvHD - Specific Core Measures
Estimated along with 95% confidence intervals (CI). Descriptive statistics will be calculated and presented for GvHD summary scores by dose level and visit.
Measured: Time from baseline to date of last follow-up or failure event, assessed at day 180
Secondary outcomes (1)
Immunomodulatory/Immuno-suppressive Effects
T, natural killer (NK)T, regulatory T cell (Treg), B, NK, dendritic cell (DC) cell subsets, cell activation status and functional potential through cytokine and chemokine expression will be identified. Descriptive statistics (with 95% confidence intervals) will be calculated at each assessment time point.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2016
- Study completionSep 2016
Why it stopped: Slow Accruals
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft Versus Host DiseaseStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Gordon Phillips, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02109809
- Sponsor's protocol ID
- IRB00026878
- Other IDs
- NCI-2014-00671, CCCWFU 97114, P30CA012197
- Status last verified
- Oct 2018
- First submitted
- 8 Apr 2014
- Last updated
- 23 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study: Low-Dose Total Lymphoid Irradiation in the Treatment of Refractory Chronic Graft Versus Host Disease
- ClinicalTrials.gov ID
- NCT02109809
- Acronym / sponsor ID
- IRB00026878
- Conditions
- Graft Versus Host Disease
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accruals
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jul 2014
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 10 Apr 2014 (estimated)
- Results
- Posted 23 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of low-dose total lymphoid irradiation (LD-TLI) in treating patients with chronic graft-versus-host disease that has not responded to treatment with steroids. LD-TLI is a procedure in which all of the body's major lymph nodes are treated with small doses of radiation in order to reset the dysfunctional immune system. LD-TLI may work as a treatment for graft-versus-host disease caused by a bone marrow or stem cell transplant.
Detailed description
PRIMARY OBJECTIVES:
- To determine the safety of total lymphoid irradiation (TLI) in cohorts of a selected population of refractory chronic graft-versus-host disease (GvHD) patients, given to cohorts with a total cumulative doses of TLI of 100, 150, 200, 250 or 300 centigray (cGy).
SECONDARY OBJECTIVES:
- To evaluate the efficacy (failure free survival [FFS] at 6 months) of this therapy in the study population.
II. Approximate the efficacy at different dose levels using the GvHD summary scores.
TERTIARY OBJECTIVES:
- Determine the effect of this therapy on relevant subpopulations of immune cells in an attempt to elucidate a mechanism of action.
OUTLINE: This is a dose-escalation study.
Patients undergo LD-TLI daily for 1-2 days.
After completion of study treatment, patients are followed up on day 45, at 3 and 6 months, at 1 year, and then every 6 months thereafter.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Supportive Care (TLI) | Experimental | Radiation: total nodal irradiation, Other: laboratory biomarker analysis, Other: questionnaire administrationPatients undergo LD-TLI daily for 1-2 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients may have received a prior allogeneic hematopoietic stem cell transplant (alloHSCT) for any indication and from any donor
- Patients must have a diagnosis of cGvHD, in accordance with National Institutes of Health (NIH) guidelines; patients with "overlap syndrome" are also eligible; NOTE: Patients with recurrent, late onset and/or persistent acute GvHD (alone) are not eligible
- Patients with chronic GvHD who have been exposed to two or more lines of therapy, including at least one of which was composed of a glucocorticoid and a calcineurin inhibitor are eligible.
- Patients must have active, but not rapidly progressive, refractory cGvHD; any degree of severity (as per NIH criteria) and/or pattern of organ involvement may be considered; that said, patients with more severe and/or extensive chronic GvHD are expected to be the usual candidates for therapy
- As above, GvHD should be controlled to a degree that would potentially allow no additional requirement for systemic IST before and following TLI =< -15 and >= day (d) +45, respectively
Key exclusion criteria (2 listed)
- Patients with evidence of persistent or active malignancy or uncontrolled infection at the time of study entry
- Patients who are pregnant or breastfeeding
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 |
|---|---|---|
| total nodal irradiationAlso: TLI, total lymphoid irradiationUndergo TLI | Radiation | Supportive Care (TLI) |
| laboratory biomarker analysisCorrelative studies | Other | Supportive Care (TLI) |
| questionnaire administrationAncillary studies | Other | Supportive Care (TLI) |
Primary outcome
Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0
Time frame: At day 180
Toxicities (grade 2 and higher) will be reported as number of occurrences.
Failure Free Survival (FFS) as Assessed by Scoring for Chronic GvHD - Specific Core Measures
Time frame: Time from baseline to date of last follow-up or failure event, assessed at day 180
Estimated along with 95% confidence intervals (CI). Descriptive statistics will be calculated and presented for GvHD summary scores by dose level and visit.
1 secondary outcome
Immunomodulatory/Immuno-suppressive Effects
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Graft Versus Host Disease
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
Active, not recruitingPhase 1/2
Alvelestat (MPH966), an Oral Neutrophil Elastase Inhibitor, in Bronchiolitis Obliterans Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation
Chronic Graft vs Host Disease, Chronic Graft-Versus-Host Disease
Not yet recruiting
A New ECP Protocol for the Treatment of cGVHD
Chronic Graft Versus Host Disease
RecruitingPhase 1/2
The Lowest Effective Dose of Post-Transplantation Cyclophosphamide in Combination With Sirolimus and Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning and Peripheral Blood Stem Cell Transplantation
Peripheral Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation
Recruiting
Effect of Anomia Rehabilitation Combined With Metacognitive Training in Patients With Chronic Vascular Aphasia
Aphasia, Stroke
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.
Gordon Phillips principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing total nodal irradiation, laboratory biomarker analysis and questionnaire administration in people with Graft Versus Host Disease, run by Wake Forest University Health Sciences at 1 site 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 18 inclusion and 2 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: stopped early, as of the sponsor's last update on 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 23 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0 (time frame: At day 180). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Nov 2018.