Clinical trial NCT04539470: Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Participants Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Official title: A Phase Ib, Open-Label, Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Efmarodocokin Alfa in Combination With Standard of Care in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Graft-versus-host Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-09-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: This is a Phase Ib, open-label, multicenter, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetics of Efmarodocokin Alfa and to make a preliminary assessment of activity of Efmarodocokin Alfa in combination with standard-of-care (SOC) in the prevention of acute graft-versus-host disease (aGVHD) in participants undergoing allogeneic hematopoietic stem cell transplantation (HSCT).


Eligibility criteria: Inclusion Criteria:

* Eligible for hematopoietic stem cell transplantation (HSCT)
* Donor meeting human leukocyte antigen (HLA) matching criteria of HLA-matched related or HLA-matched unrelated (HLA-A, HLA-B, HLA-C, and HLA-DRB1, eight out of eight) from either peripheral blood or bone marrow stem cells and meeting donor-eligibility criteria as outlined by the U.S. Food and Drug Administration (FDA) in 21 CFR 1271 (including screening for Zika and SARS-CoV-2 exposure or infection)
* Planned HLA (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched (eight out of eight) related or planned HLA-matched (eight out of eight) unrelated HSCT, from either peripheral blood or bone marrow stem cells, for patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first complete remission (per institutional criteria) or patients with intermediate or high-risk myelodysplastic syndrome (MDS)
* Planned myeloablative conditioning regimen per institutional guidelines
* Planned aGvHD prophylaxis consisting of tacrolimus and methotrexate; in cases of tacrolimus intolerance, cyclosporine or sirolimus may be used as a substitute

Exclusion Criteria:

* Prior receipt of autologous or allogeneic HSCT
* Diagnosis of myelofibrosis or myelodysplastic/myeloproliferative overlap syndrome
* Treatment with investigational biologic or non-biologic therapy within 5 drug elimination half-lives (or within 90 days or 30 days, respectively, if half-life is unknown) prior to initiation of study drug
* Positive hepatitis B virus (HBV) or hepatitis C virus (HCV) serologies
* History of Grade \>1 cervical intraepithelial neoplasia
* A marked baseline prolongation of QT/QTc interval
* Risk factors for torsades de pointes
* Pregnant or breastfeeding
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

Primary outcomes:
measure: Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)
timeFrame: From Baseline up to 365 days
measure: Change from Baseline in Respiratory Rate Over Time
timeFrame: From Baseline up to 139 days
measure: Change from Baseline in Oxygen Saturation Over Time
timeFrame: From Baseline up to 139 days
measure: Change from Baseline in Pulse Rate Over Time
timeFrame: From Baseline up to 139 days
measure: Change from Baseline in Systolic Blood Pressure Over Time
timeFrame: From Baseline up to 139 days
measure: Change from Baseline in Diastolic Blood Pressure Over Time
timeFrame: From Baseline up to 139 days
measure: Change from Baseline in Body Temperature Over Time
timeFrame: From Baseline up to 139 days
measure: Number of Participants with Laboratory Abnormalities in Hematology Tests
timeFrame: From Baseline up to 139 days
measure: Number of Participants with Laboratory Abnormalities in Blood Chemistry Tests
timeFrame: From Baseline up to 139 days
Secondary outcomes:
measure: Serum Concentration of Efmarodocokin Alfa at Specified Timepoints
timeFrame: At predefined timepoints from Baseline until Day 139
measure: Number of Participants with Anti-Drug Antibodies (ADAs) at Baseline and During the Study
timeFrame: At predefined timepoints from Baseline until Day 139
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Miami
country: United States
facility: University of Miami Miller School of Medicine; Clinical Reseach Building
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Med Ctr; Int med/Allgy/Immun/Rheum
state: Kansas
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: