Clinical trial NCT04177004: Human Lysozyme Goat Milk for the Prevention of Graft Versus Host Disease in Patients With Blood Cancer Undergoing a Donor Stem Cell Transplant
Official title: A Randomized Pilot Study of Human Lysozyme Goat Milk in Recipients of Standard Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Allogeneic Hematopoietic Stem Cell Transplant Recipient
Hematopoietic and Lymphoid Cell Neoplasm
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-11-26
Enrollment: 43
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This phase I trial studies the side effects of human lysozyme goat milk in preventing graft versus host disease in patients with blood cancer undergoing a donor stem cell transplant. Sometimes the transplanted cells from a donor can cause an immune response against the body's own normal cells (call graft versus host disease). The goat milk in the study is from goats that have been genetically engineered to produce human lysozyme in the milk. Human lysozyme is a natural enzyme found in human milk and acts as an antimicrobial. Lysozyme is key to the digestive health of breast-fed human infants, since it helps the growth of beneficial gut bacteria and reduces the growth of bacteria that causes diarrhea and intestinal disease. Giving human lysozyme goat milk may reduce the rate of graft versus host disease in blood cancer patients undergoing a donor stem cell transplant.

Detailed description: 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 characterize and compare GVHD inflammatory biomarkers (presence, level) among hLZ-treated and untreated patients.

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

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

X. 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.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP A:

CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, undergo fractionated total body irradiation (FTBI) on days -7 to -4, and receive cyclophosphamide on days -3 to -2 or etoposide on day -3 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) three times daily (TID) 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 on days -10 to -8 and days 0 to 2 per COH SOP, undergo FTBI on days -7 to -4, and receive cyclophosphamide on days -3 to -2 or etoposide on day -3 per COH SOP 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.

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

Eligibility criteria: Inclusion Criteria:

* Documented informed consent of the participant and/or legally authorized representative
* Willingness to be followed for the planned duration of the trial (2 years)
* All subjects must have the ability to understand and the willingness to sign a written informed consent
* Karnofsky performance status \>= 60 per COH SOP
* Patients must be undergoing allogeneic hematopoietic stem cell transplantation (alloHCT) for hematologic malignancies from matched related or matched unrelated donors with 8/8 (A, B, C, DRB 1) high resolution human leukocyte antigen (HLA) donor allele matching
* Patients must be receiving a fractionated total body radiation (FTBI) based- myeloablative conditioning regimen; (acceptable conditioning regimens include total body irradiation \[TBI\] + cyclophosphamide or TBI + etoposide)
* Ejection fraction measured by echocardiogram or multi gated acquisition scan (MUGA) \> 50%
* Diffusing capacity for carbon monoxide (DLCO) adjusted for hemoglobin or forced vital capacity (FVC) \> 50% predicted
* Total serum bilirubin \< 2 times upper limit of normal
* Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 x the upper normal limit
* Alkaline phosphatase =\< 2.5 x the upper normal limit
* Measured creatinine clearance more than 60 mL/min
* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through 90 days after the last dose of protocol therapy

  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)

Exclusion Criteria:

* Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this pilot study. A legal guardian may substitute for the research participant
* Research participants receiving any other investigational agents
* Research participants with presence of other active malignancy within 2 years of study entry. Participants with history of prior malignancy treated with curative intent who achieved complete remission (CR) more than 2 years before study entry are eligible. This exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
* Research participants having any uncontrolled illness including ongoing or active infection. Research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures, or radiological evidence of infections
* Refusing to use contraception up to 90 days post-HCT
* Pregnant and/or breast feeding if a female recipient
* Lactose intolerance or intolerance to milk products
* In the opinion of the principal investigator (PI), the participant has a condition that will preclude them from complying with study treatment

Primary outcomes:
measure: Patients' ability to drink the specified daily amount of 750 ml human lysozyme goat milk (hLZ)
timeFrame: from study initiation until up to 28 days post-transplant or until discharge, whoever comes first
measure: Unacceptable toxicity
timeFrame: Up to 28 days post-transplant or date of discharge
measure: Adverse events
timeFrame: Up to 100 days post-transplant
measure: Volume of hLZ consumed
timeFrame: Up to 28 days post-transplant or date of discharge
Secondary outcomes:
measure: Cumulative incidence (CI) of chronic graft versus host disease (GVHD)
timeFrame: At 6 months
measure: Cumulative incidence (CI) of chronic GVHD
timeFrame: At 1 year
measure: Cumulative incidence (CI) of chronic GVHD
timeFrame: At 2 years
measure: CI of non-relapse mortality (NRM)
timeFrame: At 100 days
measure: CI of NRM
timeFrame: At 1 year
measure: CI of NRM
timeFrame: At 2 years
measure: CI of relapse/progression
timeFrame: At 100 days
measure: CI of relapse/progression
timeFrame: At 1 year
measure: CI of relapse/progression
timeFrame: At 2 years
measure: Gut microbiome diversity
timeFrame: Day - 8 +/- 3, day 0, day +7, day +14, day +21, day +28
measure: CI of acute graft versus host disease (aGVHD)
timeFrame: At 100 days
measure: Incidence of bloodstream infections
timeFrame: Up to 100 days
measure: Overall survival (OS)
timeFrame: At 100 days
measure: Overall survival (OS)
timeFrame: At 1 year
measure: Overall survival (OS)
timeFrame: At 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Karamjeet S Sandhu
role: PRINCIPAL_INVESTIGATOR
References: