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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Acute GvHD

Intervention / Treatment
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* Biological: ALD518
* Biological: ALD518
* Biological: ALD518


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALD518<br> | Biological: ALD518<br>* 160 mg IV q 4 weeks for 4 doses<br>Biological: ALD518<br>* 320 mg IV q 4 weeks for 4 doses<br>Biological: ALD518<br>* 640 mg IV q 4 weeks for 2 doses<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allograph, steroid refractory