AzTrials
AzTrials

Hematopoietic and Lymphoid Cell NeoplasmPhase 1NCT03531281

Human Lysozyme Goat Milk in Treating Patients With Blood Cancer Undergoing Donor Stem Cell Transplant

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Etoposide in people with Hematopoietic and Lymphoid Cell Neoplasm and Hematopoietic Cell Transplantation Recipient, run by City of Hope Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

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 transplant. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Read more about this study

Who is it for?
Ages 12 to 60 years
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
30 Dec 2018to 30 Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 to 60 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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)
Show all 14Show fewer
  • Ejection fraction measured by echocardiogram or multi gated acquisition scan (MUGA) > 45%
  • 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; the updated Schwartz formula should be used for pediatric patients (>= 5 to 12 years old)
  • 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)

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: A Randomized Pilot Study of Human Lysozyme Goat Milk in Recipients of Standard Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

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 transplant. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving human lysozyme goat milk to patients undergoing a donor stem cell transplant may stop this from happening.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the safety and feasibility of human lysozyme goat milk (hLZ) treatment by assessing type, frequency, severity, attribution, time course and duration of adverse events, including diarrhea, bloodstream/intestinal infections.

II. To evaluate the safety and feasibility of hLZ treatment by assessing patient compliance, the patients' ability to drink the specified volume (250 ml 3 x/day) of hLZ during the treatment period.

SECONDARY OBJECTIVES:

  1. 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.

  1. 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 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 arms.

ARM I:

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 infusion 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.

ARM II:

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 infusion 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 completion of study treatment, patients are followed up for up to 2 years.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Etoposide, Goat Milk, Laboratory Biomarker Analysis
Medical subject headings
Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo allo-HCT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • Goat MilkDrug

    Given human lysozyme goat milk PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PaliferminBiological

    Also called Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor

    Given IV

  • SirolimusDrug

    Also called AY 22989, RAPA, Rapamune, Rapamycin

    Given PO

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV and PO

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation

    Undergo FTBI

Study groups in NCT03531281
Study groupRoleWhat they receive
Arm I (goat milk, transplant conditioning/prophylaxis)ExperimentalCONDITIONING: 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 infusion 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.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Goat Milk; Other: Laboratory Biomarker Analysis; Biological: Palifermin; Drug: Sirolimus; Drug: Tacrolimus; Radiation: Total-Body Irradiation
Arm II (transplant conditioning/prophylaxis)Active comparatorCONDITIONING: 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 infusion 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.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Biological: Palifermin; Drug: Sirolimus; Drug: Tacrolimus; Radiation: Total-Body Irradiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Feasibility of drinking human lysozyme goat milk (hLZ)

    Feasibility of drinking hLZ will be evaluated by assessment of patients' ability to drink the specified volume (250 ml 3 x per day) of hLZ during the safety lead-in phase.

    Measured: Up to +28 days post-transplant or date of discharge

  2. 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.

    Measured: Up to 28 days post-transplant or date of discharge

  3. 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.

    Measured: Up to 100 days post-transplant

  4. Volume of hLZ consumed

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

    Measured: Up to 28 days post-transplant or date of discharge

Secondary outcomes (15)
  1. Cumulative incidence (CI) of chronic GVHD

    Chronic graft versus host disease is scored according to NIH Consensus Staging. The first day of chronic GvHD onset will be used to calculate CI incidence curves, with relapse/death prior to onset considered competing events. CI of chronic GVHD will be estimated using the method described by Gooley et al (1999).

    Measured: At 6 months

  2. Cumulative incidence (CI) of chronic GVHD

    Chronic graft versus host disease is scored according to NIH Consensus Staging. The first day of chronic GvHD onset will be used to calculate CI incidence curves, with relapse/death prior to onset considered competing events. CI of chronic GVHD will be estimated using the method described by Gooley et al (1999).

    Measured: At 1 year

  3. Cumulative incidence (CI) of chronic GVHD

    Chronic graft versus host disease is scored according to NIH Consensus Staging. The first day of chronic GvHD onset will be used to calculate CI incidence curves, with relapse/death prior to onset considered competing events. CI of chronic GVHD will be estimated using the method described by Gooley et al (1999).

    Measured: At 2 years

  4. CI of non-relapse mortality (NRM)

    Non-relapse mortality (NRM) is defined as death occurring in a patient from causes other than relapse. NRM is measured from start of treatment until non-disease related death, or last follow-up, whichever comes first. The cumulative incidence of NRM will be calculated reflecting relapse as a competing risk. CI of NRM will be estimated using the method described by Gooley et al (1999).

    Measured: At 100 days

  5. CI of NRM

    Non-relapse mortality (NRM) is defined as death occurring in a patient from causes other than relapse. NRM is measured from start of treatment until non-disease related death, or last follow-up, whichever comes first. The cumulative incidence of NRM will be calculated reflecting relapse as a competing risk. CI of NRM will be estimated using the method described by Gooley et al (1999).

    Measured: At 1 year

  6. CI of NRM

    Non-relapse mortality (NRM) is defined as death occurring in a patient from causes other than relapse. NRM is measured from start of treatment until non-disease related death, or last follow-up, whichever comes first. The cumulative incidence of NRM will be calculated reflecting relapse as a competing risk. CI of NRM will be estimated using the method described by Gooley et al (1999).

    Measured: At 2 years

  7. CI of relapse/progression

    The event is relapse/progression. Time to this event is measured from start of treatment. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse are censored at time of last follow-up. CI of relapse/progression will be estimated using the method described by Gooley et al (1999).

    Measured: At 100 days

  8. CI of relapse/progression

    The event is relapse/progression. Time to this event is measured from start of treatment. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse are censored at time of last follow-up. CI of relapse/progression will be estimated using the method described by Gooley et al (1999).

    Measured: At 1 year

  9. CI of relapse/progression

    The event is relapse/progression. Time to this event is measured from start of treatment. Death without relapse/progression is considered a competing risk. Surviving patients with no history of relapse are censored at time of last follow-up. CI of relapse/progression will be estimated using the method described by Gooley et al (1999).

    Measured: At 2 years

  10. Gut microbiome diversity

    Gut microbiome diversity will be assessed by the Simpson Index and compared between hLZ-treated/untreated patients. Association between treatment and gut microbial diversity will be assessed by Fisher's Exact test.

    Measured: Day - 8 +/- 3, Day 0, Day +7, Day +14, Day +21, Day +28

  11. CI of acute graft versus host disease (aGVHD)

    Acute graft versus host disease will be graded according to the Consensus Grading. The first day of acute GvHD onset at a certain grade will be used to calculate cumulative incidence curves for that GvHD grade; relapse/death prior to onset will be considered competing events. CI of aGVHD will be estimated using the method described by Gooley et al (1999). Association between gut microbial diversity (inverse Simpson index: high [>4], intermediate [2-4], and low [<2]) or treatment and CI of aGVHD will be assessed by Gray's test.

    Measured: At 100 days

  12. Incidence of bloodstream infections

    Incidence of bloodstream infections and infectious enterocolitis will be evaluated and a preliminary estimate of the association between gut microbiome diversity and bloodstream infections will be obtained. Association between gut microbial diversity (inverse Simpson index: high [>4], intermediate [2-4], and low [<2]) or treatment and CI of bloodstream infections will be assessed by Gray's test.

    Measured: Up to 100 days

  13. Overall survival (OS)

    Patients are considered a failure for this endpoint if they die, regardless of cause. The time to this event is the time from start of treatment until death, or last follow-up, whichever comes first. OS will be estimated using the product-limit method of Kaplan and Meier.

    Measured: At 100 days

  14. Overall survival (OS)

    Patients are considered a failure for this endpoint if they die, regardless of cause. The time to this event is the time from start of treatment until death, or last follow-up, whichever comes first. OS will be estimated using the product-limit method of Kaplan and Meier.

    Measured: At 1 year

  15. Overall survival (OS)

    Patients are considered a failure for this endpoint if they die, regardless of cause. The time to this event is the time from start of treatment until death, or last follow-up, whichever comes first. OS will be estimated using the product-limit method of Kaplan and Meier.

    Measured: At 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 May 2018
  2. Study start30 Dec 2018 (estimated)
  3. Primary completion30 Dec 2022 (estimated)
  4. Study completion30 Dec 2022 (estimated)

Why it stopped: Administratively withdrawn

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03531281
Sponsor's protocol ID
17399
Other IDs
NCI-2018-00053, 17399
Status last verified
Dec 2018
First submitted
26 Jan 2018
Last updated
7 Dec 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Etoposide in people with Hematopoietic and Lymphoid Cell Neoplasm and Hematopoietic Cell Transplantation Recipient, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility of drinking human lysozyme goat milk (hLZ) (time frame: Up to +28 days post-transplant or date of discharge). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2018.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in