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

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.

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