A Randomized Pilot Study of Human Lysozyme Goat Milk in Recipients of Standard Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Unacceptable toxicity
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Goat Milk (Drug)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Fractionated Stereotactic Radiation Therapy (Radiation)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Fractionated Stereotactic Radiation Therapy (Radiation)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Palifermin (Biological)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Palifermin (Biological)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Cyclophosphamide (Drug)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Etoposide (Drug)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Sirolimus (Drug)
Group A (conditioning, goat milk, transplant, prophylaxis)
CONDITIONING: Patients receive palifermin on days -10 to -8 and days 0 to 2, 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.
HLZ: Patients receive human lysozyme goat milk PO 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.
干预措施: Tacrolimus (Drug)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Cyclophosphamide (Drug)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Etoposide (Drug)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Sirolimus (Drug)
Group B (conditioning, transplant, prophylaxis)
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.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Unacceptable toxicity
时间窗: Up to 28 days post-transplant or date of discharge
The modified Bearman Scale will be used to define unacceptable toxicity events. Unacceptable toxicity in a given patient is defined as either of the following that are considered at least possibly related to drinking hLZ milk: GI toxicity grade III or IV per Bearman scale or inability to consume hLZ milk for \> 7 days.
Volume of hLZ consumed
时间窗: Up to 28 days post-transplant or date of discharge
Tolerability is defined as the ability to consume \>= 150 ml/day over the treatment period.
Patients' ability to drink the specified daily amount of 750 ml human lysozyme goat milk (hLZ)
时间窗: from study initiation until up to 28 days post-transplant or until discharge, whoever comes first
In the safety lead-in phase, we are going to investigate if a patient can drink the daily amount of 750 ml of hLZ.. The actual volume of milk consumed per day will be measured using graduated cups and recorded on daily basis. To calculate the average daily consumption, total volume of hLZ consumed by each patient for the whole inpatient stay will be divided by the total number of inpatient stay for that patient. Tolerable dose established based on the average daily hLZ consumption in the first 6 patients (safety lead-in) will be brought forward for additional study randomization.
Adverse events
时间窗: Up to 100 days post-transplant
Incidence and severity of adverse events will be reported according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.03. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
次要结局
- Cumulative incidence (CI) of chronic graft versus host disease (GVHD)(At 6 months)
- CI of non-relapse mortality (NRM)(At 100 days)
- CI of NRM(At 2 years)
- Cumulative incidence (CI) of chronic GVHD(At 2 years)
- CI of relapse/progression(At 2 years)
- Gut microbiome diversity(Day - 8 +/- 3, day 0, day +7, day +14, day +21, day +28)
- CI of acute graft versus host disease (aGVHD)(At 100 days)
- Incidence of bloodstream infections(Up to 100 days)
- Overall survival (OS)(At 2 years)
- Cumulative incidence (CI) of chronic GVHD(At 1 year)
- CI of NRM(At 1 year)
- CI of relapse/progression(At 100 days)
- CI of relapse/progression(At 1 year)
- Overall survival (OS)(At 100 days)
- Overall survival (OS)(At 1 year)