Human Lysozyme Goat Milk for Blood Cancer Post-Transplant Care

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Investigational agents

Disqualifiers: Active malignancy, Uncontrolled illness, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 36 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special type of goat milk modified to include human lysozyme, an enzyme that helps fight harmful bacteria. Researchers aim to determine if drinking this goat milk can reduce the risk of graft versus host disease, a condition that can occur after a stem cell transplant for blood cancer. The trial targets patients about to receive a stem cell transplant from a donor to treat their blood cancer. Participants should be able to consume milk products and be willing to follow the trial for two years. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you cannot participate if you are receiving any other investigational agents.

Is there any evidence suggesting that human lysozyme goat milk is likely to be safe for humans?

Research shows that goat milk containing human lysozyme resembles human milk and is safe to drink. This milk comes from goats genetically modified to produce human lysozyme, an enzyme in human milk that helps fight germs. Early studies indicate that this milk is safe for humans.

Since this treatment remains in the early stages of research, the main goal is to assess its safety. Although complete long-term safety information is not yet available, early studies suggest it is generally well-tolerated by participants. No serious side effects have been reported so far, but researchers will continue to monitor safety as the research progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the use of Human Lysozyme Goat Milk in blood cancer post-transplant care because it introduces a unique approach by incorporating human lysozyme, an enzyme with antimicrobial properties, directly into the patient's diet. Unlike standard care options that primarily focus on immune suppression and infection prevention through pharmaceuticals, this treatment aims to naturally enhance the patient's immune response and gut health post-transplant. By delivering this novel ingredient orally, the treatment may offer a more holistic and less invasive method to support recovery and reduce complications like infections and graft-versus-host disease.

What evidence suggests that human lysozyme goat milk might be an effective treatment for preventing graft versus host disease?

Research has shown that goat milk containing human lysozyme might reduce the risk of graft versus host disease in blood cancer patients. This condition occurs when donor cells attack the patient's body after a stem cell transplant. In this trial, some participants will receive human lysozyme goat milk as part of their treatment regimen. Lysozyme, a natural enzyme in human milk, helps maintain gut health by increasing beneficial bacteria and decreasing harmful ones. Early studies suggest that consuming this specially engineered goat milk could improve gut health and lower infection risk. This may lead to better outcomes for patients undergoing stem cell transplants. ^{1 2 3 4 5}

Who Is on the Research Team?

Karamjeet S Sandhu

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for blood cancer patients undergoing donor stem cell transplants. Participants must understand and consent to the study, have a performance status of >=60, normal liver function tests, agree to use birth control, and be free from other active cancers or infections. They should not be lactose intolerant or allergic to milk products.

Inclusion Criteria

Total serum bilirubin < 2 times upper limit of normal

I am undergoing a specific radiation therapy before a bone marrow transplant.

I am receiving a stem cell transplant from a donor who is a complete match.

Exclusion Criteria

You are not allowed to be taking any other experimental or investigational drugs as part of another study.

In the opinion of the principal investigator (PI), the participant has a condition that will preclude them from complying with study treatment

Refusing to use contraception up to 90 days post-HCT

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive palifermin, undergo fractionated total body irradiation, and receive cyclophosphamide or etoposide as per standard operating procedure

7 days

Daily visits for treatment administration

Treatment

Patients receive human lysozyme goat milk orally three times daily and undergo stem cell transplant

36 days

Daily visits for monitoring and treatment

GVHD Prophylaxis

Patients receive tacrolimus and sirolimus daily to prevent graft versus host disease

Up to 100 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Human Lysozyme Goat Milk

Trial Overview The trial is testing human lysozyme goat milk's ability to prevent graft versus host disease post-transplant. The milk comes from genetically modified goats producing human lysozyme—an enzyme that supports gut health by promoting beneficial bacteria growth.

How Is the Trial Designed?

Group I: Group A (conditioning, goat milk, transplant, prophylaxis) Experimental Treatment 8 Interventions

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.

Group II: Group B (conditioning, transplant, prophylaxis) Active Control 7 Interventions

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.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Transgenic goat milk expressing recombinant human lysozyme (rhLZ) showed similar physicochemical properties to non-transgenic goat milk and human milk, with effective concentrations of rhLZ that could enhance immune response against certain pathogens.

The rhLZ milk exhibited antibacterial activity against specific bacteria, improved cell migration in intestinal epithelial cells, and showed potential as a nutraceutical to enhance health and nutrition quality in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Milk from transgenic goat expressing human lysozyme for recovery and treatment of gastrointestinal pathogens. Carneiro, IS., Menezes, JNR., Maia, JA., et al.[2018]

Lysozymes are powerful enzymes that not only kill bacteria by breaking down their cell walls but also play a crucial role in the innate immune system, helping to fight infections and inflammation.

Recent studies suggest that lysozymes may have anti-cancer properties, potentially enhancing immune responses against tumors, and they could serve as useful markers for cancer prognosis and recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Insights Into the Prognostic and Therapeutic Applications of Lysozymes. Jiang, L., Li, Y., Wang, L., et al.[2021]

Transgenic cloned cows were successfully created to produce recombinant human lysozyme (rhLZ) in their milk, achieving concentrations of up to 3149.19 mg/L, which is significant for potential therapeutic use.

The rhLZ produced in cow milk exhibited similar molecular weight and enzymatic activity to natural human lysozyme, indicating that this method could be a viable approach for large-scale production of this important immune protein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-scale production of functional human lysozyme from marker-free transgenic cloned cows. Lu, D., Liu, S., Ding, F., et al.[2018]

In a study involving C57BL/10 mice with fibrosarcoma, pre-immunization with human lysozyme (HLZM) significantly increased protection against tumor development, with 42-44% of mice remaining tumor-free compared to 14-22% with standard immunization methods.

The effectiveness of HLZM in enhancing tumor immunogenicity was shown to depend on its enzymatic activity, indicating a potential mechanism for improving cancer immunotherapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lysozyme enhancement of tumor cell immunoprotection in a murine fibrosarcoma. Warren, JS., Rinehart, JJ., Zwilling, BS., et al.[2007]

Genetically engineered goats producing higher levels of lysozyme in their milk did not negatively impact the growth of lactic acid bacteria (LAB) during cheese-making, suggesting that this modification is safe for the cheese production process.

While there were no significant differences in LAB counts in the early stages of cheese production, a notable decrease in LAB was observed in cheese made from transgenic goat milk by day 6, indicating potential benefits for product shelf life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of human lysozyme transgenic goat milk in cheese making: effects on lactic acid bacteria performance. Scharfen, EC., Mills, DA., Maga, EA.[2007]

Young pigs fed milk from transgenic goats producing human lysozyme (hLZ-milk) showed faster recovery from E. coli-induced diarrhea compared to those fed regular goat milk, with improved fecal consistency and activity levels.

The hLZ-milk group exhibited significant reductions in pro-inflammatory cytokines and better intestinal health, indicating that hLZ-milk may be an effective treatment for diarrhea in young children, similar to its protective role in breastfeeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consuming transgenic goats' milk containing the antimicrobial protein lysozyme helps resolve diarrhea in young pigs. Cooper, CA., Garas Klobas, LC., Maga, EA., et al.[2021]

Goat milk, especially from transgenic goats expressing human lysozyme (HLZ), significantly enhances the repair of intestinal barrier function damaged by Enteroaggregative Escherichia coli (EAEC), as shown in various cell assays.

Both HLZ transgenic and control goat milk improved cell proliferation and viability while reducing bacterial adhesion and colonization, with HLZ milk providing superior benefits in cellular migration and protection against EAEC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Goat milk with and without increased concentrations of lysozyme improves repair of intestinal cell damage induced by enteroaggregative Escherichia coli. Carvalho, EB., Maga, EA., Quetz, JS., et al.[2021]

Transgenic cloned pigs were successfully created to produce high levels of recombinant human lysozyme (rhLZ) in their milk, reaching concentrations of 2759.6 mg/L, which is significantly higher than the trace amounts found in pig milk.

The rhLZ in the milk not only inhibited the growth of harmful bacteria like E. coli but was also safely absorbed by piglets' intestines without causing allergic reactions, suggesting its potential for enhancing immune protection in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Production of transgenic-cloned pigs expressing large quantities of recombinant human lysozyme in milk. Lu, D., Liu, S., Shang, S., et al.[2018]

Transgenic goats were successfully created to produce high levels of recombinant human lysozyme (rhLZ) in their milk, achieving concentrations up to 6.2 g/L, which is significantly higher than that found in human milk.

The rhLZ produced from goat milk demonstrated similar properties and antibacterial effectiveness as natural human lysozyme, indicating its potential for use in biopharmaceutical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large-scale production of functional human lysozyme in transgenic cloned goats. Yu, H., Chen, J., Liu, S., et al.[2018]

Oral administration of 100 mg/kg/day of hen egg-white lysozyme for 8 days significantly enhances the effectiveness of 5-fluorouracil (5-FU) in treating advanced mammary carcinomas in mice, improving tumor growth control and reducing lung metastasis.

Lysozyme appears to boost immune responses by correcting lymphocyte activity, suggesting that it can enhance the body's immune system to support cancer treatment, particularly in conjunction with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lysozyme stimulates lymphocyte response to ConA and IL-2 and potentiates 5-fluorouracil action on advanced carcinomas. Sava, G., Pacor, S., Dasić, G., et al.[2013]

A human lysozyme was successfully isolated from a colon adenocarcinoma cell line, accounting for about 24% of the total secreted protein, indicating its potential role in tumor biology.

The purification process involved multiple steps and confirmed the identity of the lysozyme through various biochemical methods, suggesting its significance in understanding cancer mechanisms and tumor maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lysozyme: a major secretory product of a human colon carcinoma cell line. Fett, JW., Strydom, DJ., Lobb, RR., et al.[2019]

Lactoferrin (Lf) from colostrum, particularly from commercial sources, showed the strongest anticancer effects against breast cancer cell lines (MDA-MB-231 and MCF-7) in a study using a standardized dose of 750 µg/mL over 48 and 72 hours.

The study demonstrated that Lf can inhibit cancer cell growth by inducing apoptosis and affecting key genes related to tumor progression and survival, highlighting its potential as an anticancer agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Milk Colostrum Derived Lactoferrin of Sahiwal (Bos indicus) and Karan Fries (Cross-Bred) Cows for Its Anti-Cancerous Potential. Sharma, A., Shandilya, UK., Sodhi, M., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03531281

NCT03531281 | Human Lysozyme Goat Milk in Treating ... This randomized pilot phase I trial studies the side effects of human lysozyme goat milk in treating patients with blood cancer undergoing a donor stem cell ...

2. withpower.com withpower.com/trial/phase-1-hematologic-neoplasms-3-2021-e521c?condition=&query=Palifermin&overallStatus=Recruiting&hasNoPlacebo=false

Human Lysozyme Goat Milk for Blood Cancer Post ... Giving human lysozyme goat milk may reduce the rate of graft versus host disease in blood cancer patients undergoing a donor stem cell transplant. Show more.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-06454

Human Lysozyme Goat Milk for the Prevention of Graft ... Giving human lysozyme goat milk may reduce the rate of graft versus host disease in blood cancer patients undergoing a donor stem cell transplant.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04177004?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D((AMYLOIDOSIS,%20HEREDITARY%20SYSTEMIC)%20OR%20(LYZ)))&rank=10

Human Lysozyme Goat Milk for the Prevention of Graft ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. app.trialscreen.org app.trialscreen.org/trials/phase-1-allogeneic-hematopoietic-stem-cell-transplant-recipient-human-lysozyme-trial-nct04177004

Human Lysozyme Goat Milk for the Prevention of Graft ... Potential benefits include reduced risk of graft versus host disease and infections, improved gut health and microbiome, and better overall outcomes after stem ...