Clinical trial NCT02109809: Low-Dose Total Lymphoid Irradiation in Treating Patients With Refractory Chronic Graft-versus-Host Disease After Donor Stem Cell Transplant
Official title: A Phase I Study: Low-Dose Total Lymphoid Irradiation in the Treatment of Refractory Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Graft Versus Host Disease
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-04-10
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0
timeFrame: At day 180
measure: Failure Free Survival (FFS) as Assessed by Scoring for Chronic GvHD - Specific Core Measures
timeFrame: Time from baseline to date of last follow-up or failure event, assessed at day 180
Secondary outcomes:
measure: Immunomodulatory/Immuno-suppressive Effects
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Gordon Phillips
role: PRINCIPAL_INVESTIGATOR
References: