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

NCT04177004 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: 19214NCI-2019-06454
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Allogeneic Hematopoietic Stem Cell Transplant Recipient

Outcome Measures

Primary Outcomes (4)

• Patients' ability to drink the specified daily amount of 750 ml human lysozyme goat milk (hLZ)

  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.

  from study initiation until up to 28 days post-transplant or until discharge, whoever comes first

• Unacceptable toxicity

  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.

  Up to 28 days post-transplant or date of discharge

• Adverse events

  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.

  Up to 100 days post-transplant

• Volume of hLZ consumed

  Tolerability is defined as the ability to consume \>= 150 ml/day over the treatment period.

  Up to 28 days post-transplant or date of discharge

Secondary Outcomes (15)

• Cumulative incidence (CI) of chronic graft versus host disease (GVHD)

  At 6 months

• Cumulative incidence (CI) of chronic GVHD

  At 1 year

• Cumulative incidence (CI) of chronic GVHD

  At 2 years

• CI of non-relapse mortality (NRM)

  At 100 days

• CI of NRM

  At 1 year

Study Arms (2)

Group A (conditioning, goat milk, transplant, prophylaxis)

EXPERIMENTAL

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Etoposide; Radiation: Fractionated Stereotactic Radiation Therapy; Drug: Goat Milk; Biological: Palifermin; Drug: Sirolimus; Drug: Tacrolimus

Group B (conditioning, transplant, prophylaxis)

ACTIVE COMPARATOR

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Etoposide; Radiation: Fractionated Stereotactic Radiation Therapy; Biological: Palifermin; Drug: Sirolimus; Drug: Tacrolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allo-HCT

Also known as: Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Fractionated Stereotactic Radiation Therapy RADIATION

Undergo FTBI

Also known as: Fractionated Stereotactic Radiotherapy

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Goat Milk DRUG

Given human lysozyme goat milk PO

Group A (conditioning, goat milk, transplant, prophylaxis)

Palifermin BIOLOGICAL

Given IV

Also known as: Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor, rhKGF, rhu Keratinocyte Growth Factor

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Sirolimus DRUG

Given PO

Also known as: AY 22989, RAPA, Rapamune, RAPAMYCIN, SILA 9268A, WY-090217

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Tacrolimus DRUG

Given IV and PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Group A (conditioning, goat milk, transplant, prophylaxis); Group B (conditioning, transplant, prophylaxis)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Cyclophosphamide; Etoposide; Fibroblast Growth Factor 7; Sirolimus; Tacrolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Macrolides; Lactones

Study Officials

• Karamjeet S Sandhu

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: November 26, 2019
• Study Start: April 30, 2021
• Primary Completion (Estimated): October 27, 2026
• Study Completion (Estimated): October 27, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)