Acute GvHD
Conditions
Keywords
allograph, steroid refractory
Brief summary
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.
Interventions
BIOLOGICALALD518
160 mg IV q 4 weeks for 4 doses
Sponsors
CSL Behring
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 20 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
The trial was terminated after only 3 participants received the 160 mg dose.
Participants by arm
| Arm | Count |
|---|---|
| ALD518 ALD518: 160 mg IV q 4 weeks for 4 doses | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
Baseline characteristics
| Characteristic | ALD518 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 3 / 3 |
Outcome results
Primary
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.
Time frame: Week 4
Population: 2 of 3 participants died before Week 4 so could not be assessed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALD518 | Number of Participants With Acute GVHD Response at Week 4 | 0 participants |
Primary
Number of Participants With Adverse Events, Including Infections and Loss of Engraftment
Time frame: Through Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALD518 | Number of Participants With Adverse Events, Including Infections and Loss of Engraftment | 3 participants |
Secondary
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.
Time frame: Up to 20 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ALD518 | Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Participant 1 (Day 0) | 93 score on a scale |
| ALD518 | Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Participant 1 (Week 4) | 96 score on a scale |
| ALD518 | Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Participant 1 (Week 12) | 102 score on a scale |
| ALD518 | Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Participant 1 (Week 20) | 113 score on a scale |
| ALD518 | Change in Patient Reported Outcomes as Measured by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) Questionnaire Score | Participant 2 (Day 0) | 55 score on a scale |
Secondary
Number of Participants With Overall Survival
Time frame: Through Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALD518 | Number of Participants With Overall Survival | 1 participants |
Secondary
Number of Participants With Relapse of Underlying Malignant Disease
Time frame: Through Week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ALD518 | Number of Participants With Relapse of Underlying Malignant Disease | 0 participants |