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

Primary Purpose

Graft Versus Host Disease

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

total nodal irradiation

laboratory biomarker analysis

questionnaire administration

About this trial

This is an interventional supportive care trial for Graft Versus Host Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Comprehensive Cancer Center of Wake Forest University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive Care (TLI)

Arm Description

Patients undergo LD-TLI daily for 1-2 days.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02109809

First Posted

April 8, 2014

Last Updated

October 24, 2018

Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT02109809

Brief Title

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

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Terminated

Why Stopped

Slow Accruals

Study Start Date

July 2014 (undefined)

Primary Completion Date

September 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Versus Host Disease

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Supportive Care (TLI)

Arm Type

Experimental

Arm Description

Patients undergo LD-TLI daily for 1-2 days.

Intervention Type

Radiation

Intervention Name(s)

total nodal irradiation

Other Intervention Name(s)

TLI, total lymphoid irradiation

Intervention Description

Undergo TLI

Intervention Type

Other

Intervention Name(s)

laboratory biomarker analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

questionnaire administration

Intervention Description

Ancillary studies

Primary Outcome Measure Information:

Title

Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0

Description

Toxicities (grade 2 and higher) will be reported as number of occurrences.

Time Frame

At day 180

Title

Failure Free Survival (FFS) as Assessed by Scoring for Chronic GvHD - Specific Core Measures

Description

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

Secondary Outcome Measure Information:

Title

Immunomodulatory/Immuno-suppressive Effects

Description

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gordon Phillips

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Comprehensive Cancer Center of Wake Forest University

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

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

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