Graft Versus Host Disease
Conditions
Brief 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. 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: I. 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: I. 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: I. 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.
Interventions
RADIATIONtotal nodal irradiation
Undergo TLI
OTHERlaboratory biomarker analysis
Correlative studies
OTHERquestionnaire administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 * 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
Exclusion criteria
* Patients with evidence of persistent or active malignancy or uncontrolled infection at the time of study entry * Patients who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0 | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunomodulatory/Immuno-suppressive Effects | Up to 1 year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Supportive Care (TLI) Patients undergo LD-TLI daily for 1-2 days.
total nodal irradiation: Undergo TLI
laboratory biomarker analysis: Correlative studies
questionnaire administration: Ancillary studies | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Supportive Care (TLI) |
|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 16 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
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.
Time frame: Time from baseline to date of last follow-up or failure event, assessed at day 180
Population: Only 1 participant on study treatment and there are concerns of patient privacy.
Primary
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.
Time frame: At day 180
Population: Only 1 participant on study treatment and there are concerns of patient privacy.
Secondary
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.
Time frame: Up to 1 year
Population: Only 1 participant on study treatment and there are concerns of patient privacy.