MPH966 for Prevention of Graft-versus-host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

NCT ID: NCT03986086

Last Updated: 2020-03-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2023-12-31

Brief Summary

The purpose of this study is evaluate the safety and tolerability of MPH966, a neutrophil elastase inhibitor, and its ability to prevent graft-versus-host disease after hematopoietic stem cell transplant.

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.

Conditions

Hematologic Malignancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

MPH966

Participants receive MPH966 at RP2D tablet orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.

Group Type: EXPERIMENTAL

MPH966

Intervention Type: DRUG

RP2D tablet

Placebo

Participants receive MPH placebo tablet matching MPH966 orally twice daily from the start of conditioning chemotherapy through 45 days post transplant.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

MPH966 placebo table

Interventions

MPH966

RP2D tablet

Intervention Type: DRUG

Placebo

MPH966 placebo table

Intervention Type: DRUG

Other Intervention Names

alvelestat

Eligibility Criteria

Inclusion Criteria

1. Provision of written informed consent prior to any study specific procedures

2. 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.

3. Plan to receive a myeloablative conditioning regimen (see 4.3.1).

4. Plan to receive GVHD prophylaxis with tacrolimus and methotrexate.

5. Having a donor who is a 10 of 10 HLA match;

6. Karnofsky Performance Scale KPS ≥60

7. 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

1. If female, pregnant or nursing.

2. Life expectancy <6 months

3. 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

4. Clinically significant active infection within 1 week of starting study drug

5. Any of the following organ system function criteria:

1. 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

2. Renal: Creatinine clearance (CLcr) ≤ 60 mL/min as estimated by the Cockcroft-Gault equation

3. 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)

5. 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

6. 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

7. Prior (within 30 days) or concomitant use of another neutrophil elastase inhibitor (e.g. alpha-1 antitrypsin)

8. Plan for in vivo or ex vivo T cell depletion.

9. 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

1. 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.

2. Enrollment in biorepository or supportive care trials that do not involve investigational drugs or devices is allowed

10. 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

11. 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mereo BioPharma

INDUSTRY

Sponsor Role: collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

Nelson Chao

OTHER

Sponsor Role: lead

Responsible Party

Nelson Chao

Donald D. and Elizabeth G. Cooke Cancer Research Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Anthony Sung, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University Health System (DUHS)

Locations

Duke University Adult Bone Marrow Transplant Clinic

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00102362

Identifier Type: -

Identifier Source: org_study_id