- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03986086
MPH966 for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 1/2 Study of MPH966, an Oral Neutrophil Elastase Inhibitor, for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Phase 1 is a 3+3 dose escalation study to determine the safety and recommended phase 2 dose (RP2D) of MPH966 in patients undergoing allogeneic hematopoietic stem cell transplantation (HCT). We will evaluate up to 4 doses: 60 mg po bid, 120 mg po bid, 180 mg po bid, and 240 mg po bid. Safety, tolerability, and efficacy will be assessed in real time and pharmacokinetics and pharmacodynamics after each dose cohort before escalating to the next cohort.
Phase 2 is a randomized, double-blind, placebo-controlled study to determine the clinical efficacy of MPH966 vs. placebo in preventing acute graft-versus-host disease (GVHD) after HCT, using the RP2D as determined by the phase 1 trial.
Study Type
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27705
- Duke University Adult Bone Marrow Transplant Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provision of written informed consent prior to any study specific procedures
- Plan to undergo allogeneic HCT for any cancer or non-cancer illness with a planned cell dose of ≥2 x 106 CD34/kg using peripheral blood stem cells.
- Plan to receive a myeloablative conditioning regimen (see 4.3.1).
- Plan to receive GVHD prophylaxis with tacrolimus and methotrexate.
- Having a donor who is a 10 of 10 HLA match;
- Karnofsky Performance Scale KPS ≥60
- Willing to abstain from sexual activity or use two methods of birth control while on study drug and for 5 half-lives (4 days) after last dose.
Exclusion Criteria:
- If female, pregnant or nursing.
- Life expectancy <6 months
- Other malignancy or neoplastic disease (i.e. aside from the malignancy for which they are undergoing HCT) within the past 5 years with the exception of treated basal/squamous cell skin carcinoma or treated cervical cancer in situ
- Clinically significant active infection within 1 week of starting study drug
Any of the following organ system function criteria:
- Cardiac: Ejection fraction ≤40% or myocardial infarction within 6 months of transplant or QTc >450 msec for males and >470 msec for females or other EKG abnormality which in the opinion of the investigator may put the subject at risk or interfere with study assessments
- Renal: Creatinine clearance (CLcr) ≤ 60 mL/min as estimated by the Cockcroft-Gault equation
- Pulmonary: FEV1, FVC, or corrected DLCO ≤40% predicted (forced expiratory volume in 1 second; forced vital capacity; and diffusing capacity of the lung for carbon monoxide, respectively)
- Hepatic: Total bilirubin >1.5 x (in the absence of known inherited hyperbilirubinemia, e.g. Gilbert's) and/or aspartate transaminase (AST)/alanine transaminase (ALT) >3 x upper limit of institutional normal for age (grade 2 or higher) and/or INR >1.5 (unless on anticoagulant), or history or evidence of cirrhosis (e.g. esophageal varices, ascites, or hepatic encephalopathy) or other chronic liver disease (e.g. Wilson's disease, autoimmune liver disease, primary biliary cirrhosis, etc.). Abnormalities in platelet number or albumin will not be considered exclusion criteria given that these are often due to the hematologic malignancy for which the patient is undergoing HCT rather than actual liver dysfunction
- Uncontrolled infection, including detection of hepatitis B virus (HBV) or hepatitis C virus (HCV) by serology or nucleic acid testing or HIV by polymerase chain reaction (PCR)
i. Treated HBV/HCV/HIV with documented clearance is ok f. Other significant organ dysfunction (cardiac, pulmonary, renal, metabolic or central nervous system) that is uncontrolled and may interfere with study completion
- Any significant medial history of alcohol abuse within 3 months of starting study drug and/or unwillingness to abstain for the duration of the study and follow up periods
- Prior (within 30 days) or concomitant use of another neutrophil elastase inhibitor (e.g. alpha-1 antitrypsin)
- Plan for in vivo or ex vivo T cell depletion.
Participated in another clinical study involving an investigational drug or device within 30 days or 5 half-lives prior to planned start of MPH966/placebo, or scheduled to participate in another clinical study involving an investigational drug or device within Day 100 of transplant
- If the patient develops GVHD within the first 100 days, they are allowed to enroll on trials of investigational drugs to treat GVHD provided they come off of this study.
- Enrollment in biorepository or supportive care trials that do not involve investigational drugs or devices is allowed
- Any clinically relevant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis at visit, which in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study
- Low or intermediate risk acute leukemia in first complete remission, chronic myeloid leukemia in first chronic phase, and any benign (non-malignant) disorders (phase 1 dose-escalation portion only)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: MPH966
Participants receive MPH966 at RP2D tablet orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.
|
RP2D tablet
Other Names:
|
PLACEBO_COMPARATOR: Placebo
Participants receive MPH placebo tablet matching MPH966 orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.
|
MPH966 placebo table
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of grade 2-4 acute Graft vs Host Disease (GVHD) requiring systemic therapy
Time Frame: day 100
|
day 100
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of grade 2-4 acute GVHD
Time Frame: day 100
|
day 100
|
|
Incidence of grade 3-4 acute GVHD
Time Frame: day 100
|
day 100
|
|
Incidence of grade 2-4 acute GVHD
Time Frame: month 6
|
month 6
|
|
Incidence of grade 3-4 acute GVHD
Time Frame: month 6
|
month 6
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop grade 2-4 acute GVHD by visit
Time Frame: day 0 and 100 days, 6 months
|
day 0 and 100 days, 6 months
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop grade 3-4 acute GVHD by visit
Time Frame: Day 0 and day 100, month 6
|
Day 0 and day 100, month 6
|
|
Incidence of chronic GVHD
Time Frame: month 6
|
month 6
|
|
Incidence of chronic GVHD
Time Frame: month 12
|
month 12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop chronic GVHD
Time Frame: Day 0 and month 6, 12
|
Time to event distributions estimated by the Kaplan-Meier method
|
Day 0 and month 6, 12
|
Incidence of GVHD-free survival
Time Frame: month 6
|
GVHD-free survival is defined as freedom from GVHD requiring systemic steroids
|
month 6
|
Incidence of GVHD-free survival
Time Frame: month 12
|
GVHD-free survival is defined as freedom from GVHD requiring systemic steroids
|
month 12
|
Incidence of relapse-free survival
Time Frame: month 6
|
Relapse-free survival is defined as freedom from relapse
|
month 6
|
Incidence of relapse-free survival
Time Frame: month 12
|
Relapse-free survival is defined as freedom from relapse
|
month 12
|
Incidence of bacterial infections
Time Frame: Day 100
|
Day 100
|
|
Incidence of fungal infections
Time Frame: Day 100
|
Day 100
|
|
Incidence of viral infections
Time Frame: Day 100
|
Day 100
|
|
Incidence of overall infections
Time Frame: Day 100
|
Day 100
|
|
Incidence of bacterial infections
Time Frame: 6 months
|
6 months
|
|
Incidence of fungal infections
Time Frame: month 6
|
month 6
|
|
Incidence of viral infections
Time Frame: month 6
|
month 6
|
|
Incidence of overall infections
Time Frame: month 6
|
month 6
|
|
Incidence of bacterial infections
Time Frame: month 12
|
month 12
|
|
Incidence of fungal infections
Time Frame: month 12
|
month 12
|
|
Incidence of viral infections
Time Frame: month 12
|
month 12
|
|
Incidence of overall infections
Time Frame: month 12
|
month 12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop bacterial infections
Time Frame: Day 0 and day 100, month 6,12
|
Day 0 and day 100, month 6,12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop fungal infections
Time Frame: Day 0 and day 100, month 6,12
|
Day 0 and day 100, month 6,12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop viral infections
Time Frame: Day 0 and day 100, month 6,12
|
Day 0 and day 100, month 6,12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who develop overall infections
Time Frame: Day 0 and day 100, month 6,12
|
Day 0 and day 100, month 6,12
|
|
Incidence of relapse
Time Frame: month 6
|
month 6
|
|
Incidence of relapse
Time Frame: month 12
|
month 12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who relapse
Time Frame: Day 0 and month 6,12
|
Day 0 and month 6,12
|
|
Incidence of non-relapse mortality
Time Frame: month 6
|
Non-relapse mortality is defined as death while in remission from the primary disease
|
month 6
|
Incidence of non-relapse mortality
Time Frame: month 12
|
Non-relapse mortality is defined as death while in remission from the primary disease
|
month 12
|
Kaplan-Meier analysis of time-to-event: percentage of participants who experience non-relapse mortality
Time Frame: Day 0 and month 6,12
|
Non-relapse mortality is defined as death while in remission from the primary disease
|
Day 0 and month 6,12
|
Incidence of hospital re-admission
Time Frame: Day 100
|
Day 100
|
|
Incidence of hospital re-admission
Time Frame: month 6
|
month 6
|
|
Incidence of hospital re-admission
Time Frame: month 12
|
month 12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who are re-admitted to the hospital
Time Frame: Day 0 and day 100, month 6,12
|
Day 0 and day 100, month 6,12
|
|
Length of hospital re-admission
Time Frame: Day 100
|
Day 100
|
|
Length of hospital re-admission
Time Frame: month 6
|
month 6
|
|
Length of hospital re-admission
Time Frame: month 12
|
month 12
|
|
Incidence of intensive care unit (ICU) admission
Time Frame: Day 100
|
Day 100
|
|
Incidence of intensive care unit (ICU) admission
Time Frame: month 6
|
month 6
|
|
Incidence of intensive care unit (ICU) admission
Time Frame: month 12
|
month 12
|
|
Kaplan-Meier analysis of time-to-event: percentage of participants who are admitted to ICU
Time Frame: Day 0 and month 6,12
|
Day 0 and month 6,12
|
|
Length of intensive care unit (ICU) admission
Time Frame: Day 100
|
Day 100
|
|
Length of intensive care unit (ICU) admission
Time Frame: month 6
|
month 6
|
|
Length of intensive care unit (ICU) admission
Time Frame: month 12
|
month 12
|
|
Length of stay in days between transplant and discharge to home
Time Frame: Day 0 until discharge from hospital, up to 100 days
|
To determine the length of stay between transplant (Day 0) and discharge to home for those alive to be discharged home
|
Day 0 until discharge from hospital, up to 100 days
|
Quality of life as measured by the FACT-BMT assessment
Time Frame: day 30
|
day 30
|
|
Quality of life as measured by the FACT-BMT assessment
Time Frame: day 100
|
day 100
|
|
Quality of life as measured by the EQ 5D-5L assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the EQ 5D-5L assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the Lorig Self-Efficacy assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the Lorig Self-Efficacy assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the PG-SGA (patient-generated subjective global assessment)
Time Frame: day 30
|
day 30
|
|
Quality of life as measured by the PG-SGA (patient-generated subjective global assessment)
Time Frame: day 100
|
day 100
|
|
Quality of life as measured by the PROMIS-Depression assessment
Time Frame: day 30
|
day 30
|
|
Quality of life as measured by the PROMIS-Depression assessment
Time Frame: day 100
|
day 100
|
|
Quality of life as measured by the PROMIS-Anxiety assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the PROMIS-Anxiety assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the PROMIS-Social Isolation assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the PROMIS-Social Isolation assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the PROMIS-Emotional Support assessment
Time Frame: day 30
|
day 30
|
|
Quality of life as measured by the PROMIS-Emotional Support assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the PROMIS-Cognitive Function assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the PROMIS-Cognitive Function assessment
Time Frame: Day 100
|
Day 100
|
|
Quality of life as measured by the PROMIS-Physical Function assessment
Time Frame: Day 30
|
Day 30
|
|
Quality of life as measured by the PROMIS-Physical Function assessment
Time Frame: Day 100
|
Day 100
|
|
Rate of grade 2 or higher adverse events, causally related during treatment period
Time Frame: Day 75
|
Day 75
|
|
Rate of grade 2 or higher adverse events, causally related during follow up period
Time Frame: Year 1
|
Year 1
|
|
Rate of grade 2 or higher adverse events, non related during treatment period
Time Frame: Day 75
|
Day 75
|
|
Rate of grade 2 or higher adverse events, non related during follow up period
Time Frame: Year 1
|
Year 1
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Anthony Sung, MD, Duke University Health System (DUHS)
Study record dates
Study Major Dates
Study Start (ANTICIPATED)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Pro00102362
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Hematologic Malignancy
-
St. Jude Children's Research HospitalRecruitingRefractory Hematologic Malignancy | Relapsed Hematologic MalignancyUnited States
-
CRISPR Therapeutics AGEnrolling by invitationHematologic Malignancy | Solid MalignancyUnited States
-
Epizyme, Inc.WithdrawnRefractory Hematologic Malignancy | Relapsed Hematologic MalignancyUnited States
-
Scripps Translational Science InstituteCompleted
-
Millennium Pharmaceuticals, Inc.Completed
-
Guardant Health, Inc.CompletedNon-Hematologic MalignancyUnited States
-
CCTU- Cancer ThemeRecruitingCancer | Non-Hematologic MalignancyUnited Kingdom
-
Century Therapeutics, Inc.RecruitingHematological Malignancy | Solid Tumor MalignancyUnited States
-
Princess Maxima Center for Pediatric OncologyRecruitingRefractory Hematologic Malignancy | Relapsed Hematologic MalignancyNetherlands
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Not yet recruitingHematologic MalignancyChina
Clinical Trials on MPH966
-
National Cancer Institute (NCI)RecruitingBronchiolitis Obliterans Syndrome | Chronic Graft vs Host Disease | Chronic Graft-Versus-Host DiseaseUnited States
-
University of Alabama at BirminghamMereo BioPharmaCompleted
-
University of Alabama at BirminghamNational Institutes of Health (NIH); Mereo BioPharmaCompletedEmphysema or COPD | Alpha-1 Antitrypsin Deficiency (AATD) | Pi*ZZ, Pi*SZ, Pi*Null, Another Rare Phenotype/Genotype Known to be Associated With Either Low or Functionally Impaired AAT Including F or I MutationsUnited States
-
Mereo BioPharmaSyneos HealthCompletedEmphysema | Alpha 1-Antitrypsin Deficiency | COPDUnited Kingdom, Belgium, United States, Denmark, Canada, Sweden, Poland, Spain