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

NCT ID: NCT02109809

Last Updated: 2018-11-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-09-30

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.

Conditions

Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Supportive Care (TLI)

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

Group Type: EXPERIMENTAL

total nodal irradiation

Intervention Type: RADIATION

Undergo TLI

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

questionnaire administration

Intervention Type: OTHER

Ancillary studies

Interventions

total nodal irradiation

Undergo TLI

Intervention Type: RADIATION

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

questionnaire administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

TLI; total lymphoid irradiation

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gordon Phillips

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, United States

Countries

United States

Other Identifiers

NCI-2014-00671

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCCWFU 97114

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00026878

Identifier Type: -

Identifier Source: org_study_id