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CBM588 in Improving Clinical Outcomes in Participants Who Have Undergone Donor Hematopoietic Stem Cell Transplant

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ClinicalTrials.gov Identifier: NCT03922035
Recruitment Status : Recruiting
First Posted : April 19, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This pilot trial studies the side effects and how well CBM588 works in improving clinical outcomes in participants who have undergone donor hematopoietic stem cell transplant. Gut microbiota (formerly called gut flora) is the name given to the microbe (bacteria) population living in the intestine. Gut bacteria help the body to digest certain foods that the stomach and small intestine have not been able to digest. CBM588, may increase gut bacteria biodiversity, prevent recurrent symptoms of gastrointestinal toxicity (ranging from diarrhea to life-threatening inflammation of the colon).

Condition or disease Intervention/treatment Phase
Allogeneic Hematopoietic Stem Cell Transplant Recipient Other: Best Practice Drug: Clostridium butyricum CBM 588 Probiotic Strain Phase 1 Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Randomized Open Label Pilot Study of Clostridium Butyricum MIYAIRI 588 (CBM588) in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Actual Study Start Date : April 18, 2019
Estimated Primary Completion Date : December 24, 2021
Estimated Study Completion Date : December 24, 2021

Arm Intervention/treatment
Experimental: Arm I (CBM588)
Participants receive standard peri-/post-transplant supportive care and CBM588 PO BID from day of admission to day 28 in the absence of disease progression or unacceptable toxicity.
Other: Best Practice
Receive standard peri-/post-transplant supportive care
Other Names:
  • standard of care
  • standard therapy

Drug: Clostridium butyricum CBM 588 Probiotic Strain
Given PO
Other Names:
  • C. butyricum CBM 588 Probiotic Strain
  • C. butyricum MIYAIRI Strain
  • C. butyricum Strain MIYAIRI 588
  • CBM 588
  • CBM588
  • Clostridium butyricum MIYAIRI 588
  • Clostridium butyricum MIYAIRI 588 Probiotic Strain
  • MIYAIRI 588
  • MIYAIRI 588 Strain of C. butyricum

Active Comparator: Arm II (standard of care)
Participants receive standard peri-/post-transplant supportive care.
Other: Best Practice
Receive standard peri-/post-transplant supportive care
Other Names:
  • standard of care
  • standard therapy




Primary Outcome Measures :
  1. Incidence of adverse events scored according to the modified Bearman Scale and National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 scale [ Time Frame: From initiation of treatment until end of treatment assessed up to 100 days ]
    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.

  2. Feasibility of CBM588 [ Time Frame: 1 year ]
    Will be evaluated by assessment of patient's ability to take half of the specified dose.


Secondary Outcome Measures :
  1. Incidence and severity of adverse events assessed by modified Bearman criteria and NCI CTCAE version 5 scale [ Time Frame: Up to 2 years ]
    Will be compared among CBM588 treated and untreated patients.

  2. Overall survival [ Time Frame: Up to 2 years ]
    Will be estimated using the product-limit method of Kaplan and Meier.

  3. Cumulative incidence (CI) of chronic graft versus host disease (cGVHD) [ Time Frame: Up to 2 years ]
    Will be estimated using the method described by Gooley et al (1999).

  4. CI of acute graft versus host disease (aGVHD) [ Time Frame: Up to 2 years ]
    Will be estimated using the method described by Gooley et al (1999).

  5. CI of relapse/progression of disease [ Time Frame: Up to 2 years ]
    Will be estimated using the method described by Gooley et al (1999).

  6. Non-relapse mortality [ Time Frame: Up to 2 years ]
    Will be estimated using the method described by Gooley et al (1999).


Other Outcome Measures:
  1. Gut microbiome diversity assessed by the inverse Simpson index [ Time Frame: Up to 2 years ]
    Will be compared among CBM588?treated/untreated patients and assessed by Fisher's exact test or two-sample Wilcoxon test whenever appropriate.

  2. Gut microbiome diversity and bloodstream infection [ Time Frame: Up to 2 years ]
    Incidence of bloodstream infections and infectious enterocolitis will be evaluated and a preliminary estimate of the association between gut microbiome diversity and blood stream infections will be obtained.

  3. Gut microbiome diversity aGVHD incidence [ Time Frame: Up to 2 years ]
    Will be obtained based on: 1) evaluation and comparison of presence and levels GVHD/inflammatory biomarkers including TNFR1, ST2, Reg3 alpha, TNF?alpha, IL?8 and TGF?beta 1 between the 2 study arms, and 2) incidence, site (gastrointestinal [GI], liver, and skin), severity (grade III?IV GI toxicity per the NCI CTCAE version 5 Scale) and time to onset of aGVHD among treated and untreated patients.

  4. Levels of tryptophan metabolites [ Time Frame: Up to 2 years ]
    Presence and levels of urinary uindoxyl sulfate, tryptophan and kynurenine (markers of GI GVHD complications) will be evaluated and compared between CBM588?treated and untreated patients.

  5. Impact on regulatory T cells (T regs) [ Time Frame: Up to 2 years ]
    Presence and levels T regs will be evaluated and compared in blood samples from patients among treated and untreated patients.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative.

    • Assent, when appropriate, will be obtained per institutional guidelines.
  • Willingness to be followed for the planned duration of the trial (2 years).
  • Karnofsky performance status must be >= 60%.
  • Any hematologic disorders receiving allogeneic hematopoietic stem cell transplant with reduced intensity conditioning.
  • Planned 8/8 or 7/8 (human leukocyte antigens [HLA]-A, B, C, DR) related or unrelated donor hematopoietic cell transplantation (HCT).
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed within 30 days prior to day 1 of protocol therapy).
  • Aspartate aminotransferase (AST) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy).
  • Alanine aminotransferase (ALT) =< 2.5 x ULN (to be performed within 30 days prior to day 1 of protocol therapy).
  • Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 30 days prior to day 1 of protocol therapy).
  • Left ventricular ejection fraction (LVEF) >= 45%; Note: to be performed within 30 days prior to day 1 of protocol therapy.
  • If able to perform pulmonary function tests: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capability test (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation > 92% on room air. Note: to be performed within 30 days prior to day 1 of protocol therapy.
  • Seronegative for human immunodeficiency virus (HIV) antibody/antigen (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]). (To be performed within 30 days prior to day 1 of protocol therapy).

    • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed.
  • Meets other institutional and federal requirements for infectious disease titer requirements.

    • Note: Infectious disease testing to be performed within 30 days prior to day 1 of protocol therapy.
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. (To be performed within 30 days prior to day 1 of protocol therapy).
  • 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 at least 3 months 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.
  • Refusing to use contraception up to 90 days post-HCT.
  • Pregnant and/or breast feeding if a female recipient.
  • Patients with history of chronic intestinal disease (e.g., Crohn's disease, ulcerative colitis).
  • In the opinion of the PI, the participant has a condition that will preclude them from complying with study treatment.
  • Research participants receiving any other investigational agents.
  • Known or documented history of hypersensitivity to all the listed antibiotics, used for severe infections related to CBM588:

    • Ampicillin.
    • Chloramphenicol.
    • Clindamycin.
    • Erythromycin.
    • Metronidazole.
    • Tetracycline.
    • Vancomycin.
  • 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 response (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.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent (i.e., research participants whom are severe lactose intolerance or intolerance to milk products).
  • 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 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.
  • Any other condition that would, in the investigator?s judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures.
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03922035


Locations
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United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Ryotaro Nakamura    626-218-2405    rnakamura@coh.org   
Principal Investigator: Ryotaro Nakamura         
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ryotaro Nakamura City of Hope Medical Center

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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03922035     History of Changes
Other Study ID Numbers: 18193
NCI-2018-01886 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
18193 ( Other Identifier: City of Hope Comprehensive Cancer Center )
First Posted: April 19, 2019    Key Record Dates
Last Update Posted: August 21, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No