Low-Dose Total Lymphoid Irradiation in Treating Patients With Refractory Chronic Graft-versus-Host Disease After Donor Stem Cell Transplant

Not Applicable

Terminated

• Conditions: Graft Versus Host Disease
• Interventions: Radiation: total nodal irradiation; Other: laboratory biomarker analysis; Other: questionnaire administration

• Registration Number: NCT02109809
• Lead Sponsor: Wake Forest University Health Sciences

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-04-08
• Study First Submitted QC: 2014-04-09
• Study First Posted: 2014-04-10
• Study Start: 2014-07
• Primary Completion: 2016-09
• Study Completion: 2016-09
• Status Verified: 2018-10
• Results First Submitted: 2018-10-23
• Results First Submitted QC: 2018-10-24
• Last Update Submitted: 2018-10-24
• Results First Posted: 2018-11-23
• Last Update Posted: 2018-11-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Supportive Care (TLI)	laboratory biomarker analysis	Patients undergo LD-TLI daily for 1-2 days.
Supportive Care (TLI)	questionnaire administration	Patients undergo LD-TLI daily for 1-2 days.
Supportive Care (TLI)	total nodal irradiation	Patients undergo LD-TLI daily for 1-2 days.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Comprehensive Cancer Center of Wake Forest University; 🇺🇸 Winston-Salem, North Carolina, United States