Human Lysozyme Goat Milk for the Prevention of Graft Versus Host Disease in Patients with Blood Cancer Undergoing a Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of human lysozyme goat milk (hLZ) treatment by assessing:

Ia. Type, frequency, severity, attribution, time course and duration of adverse events, including diarrhea, bloodstream/intestinal infections.

Ib. Patients' ability to drink the specified volume (250 ml 3 x/day) of hLZ during the treatment period.

SECONDARY OBJECTIVES:

I. To compare the incidence and severity of adverse events (AE) among hLZ-treated and untreated patients, including diarrhea, bloodstream infections and intestinal infections.

II. To obtain preliminary estimates of gut microbiome diversity, as assessed by the Simpson Index, in hLZ-treated/untreated patients.

III. To compare gut microbiome diversity among hLZ-treated/untreated patients.

IV. To obtain a preliminary estimate of the possible association between gut microbiome diversity and bloodstream infections.

V. To obtain a preliminary estimate of the possible association between gut microbiome diversity and acute graft versus host disease (GVHD) cumulative incidence, including time to onset.

VI. To estimate overall survival (OS), cumulative incidence (CI) chronic GVHD of relapse/progression, and non-relapse mortality (NRM) at 100 days (excluding chronic GVHD), 6 months, 1 year and 2 years.

EXPLORATORY OBJECTIVES:

I. To characterize and compare GVHD inflammatory biomarkers (presence, level) among hLZ-treated and untreated patients.

II. To characterize and compare urinary uindoxyl sulfate, tryptophan and kynurenine levels between hLZ-treated and untreated patients.

III. To characterize and compare impact of drinking hLZ on regulatory T cells (T regs) reconstitution between hLZ-treated and untreated patients.

IV. To obtain a preliminary estimate of gut microbiome diversity and calorie intake.

V. To detect and quantify tissue injury by GvHD using whole-genome bisulfate sequencing of cell-free DNA (cfDNA).

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP A:

CONDITIONING: Patients receive palifermin 3 days prior to initiation of FTBI per COH SOP and on days 0-2, undergo fractionated total body irradiation (FTBI) per COH SOP, and receive cyclophosphamide or etoposide per City of Hope (COH) standard operating procedure (SOP) in the absence of disease progression or unacceptable toxicity.

HLZ: Patients receive human lysozyme goat milk orally (PO) 1-3 times daily on days -8 to 28 in the absence of disease progression or unacceptable toxicity.

TRANSPLANT: Patients undergo stem cell transplant on day 0.

GVHD PROPHYLAXIS: Beginning on day -2, patients receive tacrolimus and sirolimus daily per COH SOP in the absence of disease progression or unacceptable toxicity.

GROUP B:

CONDITIONING: Patients receive palifermin 3 days prior to initiation of FTBI per COH SOP and on days 0-2, undergo FTBI per COH SOP, and receive cyclophosphamide or etoposide per COH SOP in the absence of disease progression or unacceptable toxicity.

TRANSPLANT: Patients undergo stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus and sirolimus per COH SOP in the absence of disease progression or unacceptable toxicity.

Patients in both arms undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients also undergo blood, stool, and urine sample collection on the study.

After the completion of study treatment, patients are followed up for up to 30-100 days and then up to 2 years after transplant.