Trial Outcomes & Findings for Carfilzomib in Treating Patients With Chronic Graft-Versus-Host Disease (NCT NCT02491359)
NCT ID: NCT02491359
Last Updated: 2019-02-06
Results Overview
according to National Cancer Institute CTCAE, version 4.03
COMPLETED
PHASE2
20 participants
Up to 30 days following completion of study treatment
2019-02-06
Participant Flow
Participant milestones
| Measure |
Treatment (Carfilzomib)
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
16
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Carfilzomib in Treating Patients With Chronic Graft-Versus-Host Disease
Baseline characteristics by cohort
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Continuous
|
53 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Primary Disease
Acute leukemia (ALL/AML)
|
12 Participants
n=5 Participants
|
|
Primary Disease
Chronic leukemia (CML/CLL)
|
4 Participants
n=5 Participants
|
|
Primary Disease
Lymphoma (NHL/HD)
|
2 Participants
n=5 Participants
|
|
Primary Disease
Myeloma
|
1 Participants
n=5 Participants
|
|
Primary Disease
Myeloproliferative neoplasm
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 30 days following completion of study treatmentaccording to National Cancer Institute CTCAE, version 4.03
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Incidence of Adverse Events
Serious Adverse Events
|
8 participants
|
—
|
|
Incidence of Adverse Events
Non-Serious Adverse Events
|
7 participants
|
—
|
PRIMARY outcome
Timeframe: 6 monthsKaplan-Meier estimate assessed at 6 months for treatment failure, defined as requirement of an additional line of systemic immune-suppressive therapy, recurrent malignancy, or death.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Probability of Treatment Failure at 6mo
|
0.4 probability of treatment failure
|
—
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: Participants who could be evaluated for response (not missing data)
Complete response (CR) at 6 months will be determined by both clinician-defined CR, as well as separately calculated according to the proposed response definitions of the NIH Consensus Conference.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=16 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
n=16 Participants
Participants who receive carfilzomib
|
|---|---|---|
|
Complete Response Rate
partial response
|
5 participants
|
4 participants
|
|
Complete Response Rate
mixed response
|
0 participants
|
4 participants
|
|
Complete Response Rate
unchanged
|
2 participants
|
1 participants
|
|
Complete Response Rate
progressive
|
2 participants
|
0 participants
|
|
Complete Response Rate
failed
|
7 participants
|
7 participants
|
SECONDARY outcome
Timeframe: 1 yearThe cumulative incidence of non-relapse mortality (defined as death in the absence of primary malignancy relapse after transplant) and relapse (defined as hematologic relapse or any unplanned intervention to prevent progression of disease in patients with evidence (molecular, cytogenetic, flow cytometric, radiographic) of malignant disease after transplantation) will be estimated from time of study therapy initiation. These will be treated as competing-risk events, and estimated at 1 year.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse
|
7 Participants
|
—
|
SECONDARY outcome
Timeframe: 1 yearKaplain-Meier estimate assessed at 1 year for failure-free survival, defined as absence of death from any cause, relapse, or addition of secondary immune-suppressive agents.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Probability of Failure-free Survival at 1 Year
|
.32 probability of failure-free survival
|
—
|
SECONDARY outcome
Timeframe: Up to 6 monthsPopulation: Data were not collected because biologic studies were not performed. Response to study drug too minimal to justify time and expense.
The biologic impact of proteasome inhibition in the treatment of chronic GVHD will be assessed at baseline, 3 and 6 months. The association between biologic outcome measures and clinical parameters (response, treatment failure, mortality) will be studied.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 yearThe incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Incidence of Discontinuation of All Systemic Immune-suppressive Therapies
|
2 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 monthsOverall response rate (ORR) (complete response + partial response) at 6 months will be determined by both clinician-defined categories of complete response and partial response, as well as separately calculated according to the proposed response definitions of the NIH Consensus Conference.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Overall Response Rate
Physician impression ORR
|
4 participants
|
—
|
|
Overall Response Rate
NIH ORR
|
3 participants
|
—
|
SECONDARY outcome
Timeframe: 1 yearKaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Probability of Overall Survival at 1 Year
|
.65 probability of overall survival
|
—
|
SECONDARY outcome
Timeframe: 1 yearTreatment success will be estimated at 1 year with a composite outcome of complete resolution of all reversible chronic GVHD manifestations, discontinuation of all systemic immune suppressive agents, and freedom from death or primary malignancy relapse after transplant.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Treatment Success
|
0 participants
|
—
|
SECONDARY outcome
Timeframe: 1 yearAddition of therapy after carfilzomib constitutes failure, could occur at any time from baseline to 12mo.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Use of Additional Systemic Immune-suppressive Therapies
|
13 participants
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.
SF-36 subscales have min=0 and max=100; results given are actual scores at 12mo, with higher scores indicating higher quality of life.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
Norm-based physical functioning
|
36 units on a scale
Interval 14.9 to 52.8
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based role-physical score
|
33.6 units on a scale
Interval 17.7 to 54.4
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based bodily pain score
|
41.4 units on a scale
Interval 19.9 to 62.1
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based general health score
|
32.9 units on a scale
Interval 23.4 to 48.2
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based vitality score
|
42.7 units on a scale
Interval 30.2 to 64.6
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based social functioning
|
40.5 units on a scale
Interval 13.2 to 56.8
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based role-emotional score
|
40.3 units on a scale
Interval 17.0 to 55.9
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
norm-based mental health score
|
50 units on a scale
Interval 33.1 to 61.3
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
standardized physical component score
|
37 units on a scale
Interval 15.9 to 52.2
|
—
|
|
Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
standardized mental component score
|
49 units on a scale
Interval 28.6 to 64.1
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.
FACT-BMT subscales have various min/max, see below; results given are actual 12mo scores, with higher scores indicating better functioning. FACT physical well-being (0-28) FACT social/family well-being (0-28) FACT emotional well-being (0-24) FACT functional well-being (0-28) FACT Bone Marrow Transplant (BMT) subscale (0-40) FACT trial outcome index (0-96) FACT-General (G) (0-108) FACT-BMT total (0-148)
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
physical well-being
|
21.5 units on a scale
Interval 7.0 to 26.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
social/family well-being
|
21.5 units on a scale
Interval 15.0 to 28.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
emotional well-being
|
18.5 units on a scale
Interval 8.0 to 24.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
functional well-being
|
16.5 units on a scale
Interval 5.0 to 23.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
BMT subscale
|
28 units on a scale
Interval 21.0 to 33.3
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT-G
|
72.8 units on a scale
Interval 53.0 to 98.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
trial outcome index
|
65 units on a scale
Interval 39.0 to 81.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
FACT-BMT total
|
101.3 units on a scale
Interval 75.0 to 131.3
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.
HAP subscales have min=0 and max=94; results given are actual 12mo scores, with higher scores indicating better functioning. Maximum Activity Score (MAS) is highest item number answered still doing. Represents highest oxygen demanding activity that respondent still performs. Adjusted Activity Score (AAS) is MAS minus total number of stopped doing responses below MAS. A measure of usual daily activities. Modified AAS is MAS minus total number of stopped doing responses below MAS but not penalized for not doing activities not permitted post transplant. The following items are not counted against the score:11,15,19,20,22,25,34,41,42,47,49,50,52,53,54,57,72,73,77,78.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
maximum activity score
|
66 units on a scale
Interval 6.0 to 87.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
adjusted activity score
|
57 units on a scale
Interval 2.0 to 82.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
modified adjusted activity score
|
60 units on a scale
Interval 2.0 to 82.0
|
—
|
SECONDARY outcome
Timeframe: baselinePopulation: Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.
Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden.
Outcome measures
| Measure |
Treatment (Carfilzomib)
n=20 Participants
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
Response Evaluated by NIH
Participants who receive carfilzomib
|
|---|---|---|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
skin scale
|
32.5 units on a scale
Interval 0.0 to 100.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
energy scale
|
42.9 units on a scale
Interval 7.1 to 96.4
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
lung scale
|
5 units on a scale
Interval 0.0 to 30.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
eye scale
|
62.5 units on a scale
Interval 0.0 to 100.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
nutrition scale
|
5 units on a scale
Interval 0.0 to 20.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
psychological scale
|
25 units on a scale
Interval 0.0 to 66.7
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
mouth scale
|
0 units on a scale
Interval 0.0 to 75.0
|
—
|
|
Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
overall summary score
|
21.6 units on a scale
Interval 8.2 to 49.3
|
—
|
Adverse Events
Treatment (Carfilzomib)
Serious adverse events
| Measure |
Treatment (Carfilzomib)
n=20 participants at risk
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
pneumothorax
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Respiratory, thoracic and mediastinal disorders
hypoxia
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Infections and infestations
sepsis
|
10.0%
2/20 • Number of events 2 • 30 days after stopping study drug
|
|
General disorders
fever/infusion reaction
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Skin and subcutaneous tissue disorders
leg ulcers
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Respiratory, thoracic and mediastinal disorders
pneumonia
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Renal and urinary disorders
acute renal failure/sepsis
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Gastrointestinal disorders
nausea/vomitting/diarrhea
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Injury, poisoning and procedural complications
fall
|
5.0%
1/20 • Number of events 2 • 30 days after stopping study drug
|
Other adverse events
| Measure |
Treatment (Carfilzomib)
n=20 participants at risk
Patients receive carfilzomib IV over approximately 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Skin and subcutaneous tissue disorders
bullous dermatitis
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Infections and infestations
fungal lung infection
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Blood and lymphatic system disorders
decreased lymphocyte count
|
10.0%
2/20 • Number of events 2 • 30 days after stopping study drug
|
|
Gastrointestinal disorders
diarrhea
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Gastrointestinal disorders
esophageal varices
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Metabolism and nutrition disorders
hypokalemia
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Hepatobiliary disorders
increased ALT
|
5.0%
1/20 • Number of events 2 • 30 days after stopping study drug
|
|
Metabolism and nutrition disorders
intermittent hyperglycemia
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Musculoskeletal and connective tissue disorders
Left hip hemiarthroplasty
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Musculoskeletal and connective tissue disorders
myositis
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
|
Infections and infestations
rhinovirus
|
5.0%
1/20 • Number of events 1 • 30 days after stopping study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place