Exploratory Safety Study of ALD518 in Subjects With Steroid-refractory Acute Graft Versus Host Disease (GVHD) (ALD518-010)

An Exploratory Phase 1/2 Clinical Trial Evaluating ALD518 in Subjects With Glucocorticoid-Refractory Acute Graft vs. Host Disease (GVHD) After Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

The purpose of this study is to determine the safe and tolerable, biologically active, and potentially effective doses(s) of ALD518 in subjects with acute GVHD, who have failed to respond to glucocorticosteroids, for further investigation in Part B.

Study Overview

• Status: Terminated
• Conditions: Acute GvHD
• Intervention / Treatment: Biological: ALD518; Biological: ALD518; Biological: ALD518

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Glucocorticosteroid refractory acute GVHD Grade 2-4
• Prior corticosteroid therapy at > 1.0mg/kg methylprednisolone or equivalent for minimum of 3 and maximum of 14 days
• Karnofsky Performance Satus Scale ≥ 50%
• Adequate laboratory testing at screening

Exclusion Criteria:

• Subjects having Stage 1 skin acute GVHD
• Subjects with Stage 3 or 4 liver GVHD
• Prior EBV associated malignancy
• Prior or current Hepatitis B or C
• Prior or active tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALD518	Biological: ALD518; 160 mg IV q 4 weeks for 4 doses; Biological: ALD518; 320 mg IV q 4 weeks for 4 doses; Biological: ALD518; 640 mg IV q 4 weeks for 2 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Including Infections and Loss of Engraftment		Through Week 24
Number of Participants With Acute GVHD Response at Week 4	Includes calculation of both complete and partial response. Complete response = functional grade of 0 for the GVHD grading in all evaluable organs. Partial response = improvement by one or more functional grades in one or more organs involved with GVHD symptoms without progression in others, or a very good partial response which is a partial response plus all of the following: (1) skin - active erythematous rash involving less than 25% of body surface, (2) liver - total bilirubin <2 mg/dL or a 25% reduction from baseline (if >2 mg/dL), (3) gut - greater than or equal to 75% reduction in daily stool volume.	Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Relapse of Underlying Malignant Disease		Through Week 24
Number of Participants With Overall Survival		Through Week 24
Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score	The FACT-BMT assesses bone marrow transplant related concerns. The total score is the sum of sub-scale scores for 5 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, Functional Well-Being, and Bone Marrow Transplantation Subscale. Within each domain, a 5-point Likert-type scale (from 0-4) is used to measure the responses for each question. After taking into account reverse scores for questions constructed in a negative form, the subscale score for each domain is calculated by multiplying the sum of the item scores by the number of items in the subscale, then dividing by the number of items answered. The final score for FACT-BMT ranges from 0 to 148. Higher scores indicate better quality of life.	Up to 20 weeks

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Javier San Martin, MD FRCP, Alder Biopharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 6, 2012
• First Submitted That Met QC Criteria: February 7, 2012
• First Posted (Estimate): February 9, 2012

Study Record Updates

• Last Update Posted (Actual): February 17, 2021
• Last Update Submitted That Met QC Criteria: February 8, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: allograph; steroid refractory
• Other Study ID Numbers: ALD518-CLIN-010