Carfilzomib in Treating Patients With Chronic Graft-Versus-Host Disease

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02491359
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Locations: 5
• Arm: 1
• Actual Duration (Months): 34
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This pilot phase II trial studies how well carfilzomib works in treating patients with chronic graft-versus-host disease. Chronic graft-versus-host disease is a complication of a donor bone marrow or blood cell transplant, usually occurring more than three months after transplant, in which donor cells damage the host tissue. Carfilzomib may be an effective treatment for chronic graft-versus-host disease.

Condition or Disease	Intervention/Treatment	Phase
Chronic Graft Versus Host Disease	Drug: Carfilzomib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. Determine proportion of subjects with treatment failure by 6 months of carfilzomib therapy for chronic graft-versus-host disease (GVHD).

SECONDARY OBJECTIVES:

1. Determine 3 month overall (complete + partial), and complete response rate.

2. Determine 6 month overall (complete + partial), and complete response rate.

3. Report overall survival, non-relapse mortality, primary malignancy relapse, failure-free survival, treatment success, and discontinuation of immune suppression at 6 months and 1 year.

4. Examine functional outcome (2-minute walk test) and patient-reported outcomes (Lee Chronic GVHD Symptom Scale, quality of life [Short Form Health Survey (SF)-36, Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT) Questionnaire], Human Activity Profile [HAP]) at study enrollment, 6 months, and 1 year.

5. Study biologic effects of proteasome inhibition.

OUTLINE:

Patients receive carfilzomib intravenously (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.

After completion of study treatment, patients are followed up at 3, 6, and 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Carfilzomib for Treatment of Chronic Graft vs. Host Disease
• Actual Study Start Date: Nov 12, 2015
• Actual Primary Completion Date: Feb 19, 2018
• Actual Study Completion Date: Sep 12, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Carfilzomib; Given IV; Other Names: Kyprolis PR-171 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events [Up to 30 days following completion of study treatment]

   according to National Cancer Institute CTCAE, version 4.03

2. Probability of Treatment Failure at 6mo [6 months]

   Kaplan-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.

Secondary Outcome Measures

1. Complete Response Rate [Up to 6 months]

   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.

2. Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse [1 year]

   The 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.

3. Probability of Failure-free Survival at 1 Year [1 year]

   Kaplain-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.

4. Impact of Proteasome Inhibition [Up to 6 months]

   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.

5. Incidence of Discontinuation of All Systemic Immune-suppressive Therapies [1 year]

   The incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year.

6. Overall Response Rate [6 months]

   Overall 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.

7. Probability of Overall Survival at 1 Year [1 year]

   Kaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause.

8. Treatment Success [1 year]

   Treatment 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.

9. Use of Additional Systemic Immune-suppressive Therapies [1 year]

   Addition of therapy after carfilzomib constitutes failure, could occur at any time from baseline to 12mo.

10. Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) [baseline]

    SF-36 subscales have min=0 and max=100; results given are actual scores at 12mo, with higher scores indicating higher quality of life.

11. Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) [baseline]

    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)

12. Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) [baseline]

    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.

13. Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale [baseline]

    Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of chronic GVHD according to National Institutes of Health (NIH) Consensus Criteria

• May have either classic chronic GVHD or overlap subtype of chronic GVHD

• Failure of at least one prior line of systemic immune suppressive therapy for management of chronic GVHD

• Subject underwent transplantation at least 3 months prior to enrollment

• Anticipated life expectancy >= 6 months

• Alanine aminotransferase (ALT) =< 3.5 times the upper limit of normal, unless due to chronic GVHD

• Bilirubin =< 2 mg/dL, unless due to chronic GVHD

• Absolute neutrophil count (ANC) >= 1.0 × 10^9/L

• Hemoglobin >= 8 g/dL

• Platelet count >= 50 × 10^9/L

• Creatinine clearance (CrCl) >= 15 mL/minute, either measured or calculated

• Signed informed consent in accordance with federal, local, and institutional guidelines

• Females of childbearing potential (FCBP) must agree to a pregnancy test at study enrollment and to practice contraception during the study

• Male subjects must agree to practice contraception during the study

Exclusion Criteria:

• Evidence of recurrent or progressive underlying malignant disease

• Pregnant or lactating females

• Surgery within 21 days prior to enrollment

• Does not include placement of venous access device, bone marrow biopsy, GVHD diagnostic biopsy, or other routine procedures in chronic GVHD or post-transplantation care

• Uncontrolled infection within 14 days prior to enrollment

• Infection treated with appropriate antimicrobial therapy and without signs of progression/treatment failure does not constitute an exclusion criterion

• Documented human immunodeficiency virus (HIV) infection

• Active hepatitis B or C infection

• Documented unstable angina or myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or grade 3 conduction system abnormalities (unless subject has a pacemaker), left ventricular ejection fraction (LVEF) < 40%, history of torsade de pointe

• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment

• Sustained systolic blood pressure > 160 or diastolic blood pressure > 100 despite medical therapy; sustained blood sugar > 300 despite medical therapy

• Chronic hypertension or diabetes on appropriate medical therapy does not constitute an exclusion criterion

• Non-hematologic malignancy within the past 3 years with the exception of:

• Adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer

• Carcinoma in situ of the cervix or breast

• Prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen levels

• Cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study

• Significant neuropathy per Common Terminology Criteria for Adverse Events (CTCAE) version (ver.) 4.03 or current version (grade 3 and above, or grade 2 with pain) within 14 days prior to enrollment

• History of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)

• Contraindication to all available herpes simplex virus (HSV)/varicella prophylactic antiviral drugs

• Pleural effusions requiring thoracentesis, or ascites requiring paracentesis, within 14 days prior to enrollment

• Any other clinically significant medical or psychological disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

• New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment

• Treatment with a non-Food and Drug Administration (FDA) approved drug in the previous 4 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
3	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
4	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
5	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Stephanie Lee, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 9, 2016

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02491359
• Other Study ID Numbers: 9228; NCI-2015-00809; 9228.00; 9228; P30CA015704
• First Posted: Jul 8, 2015
• Last Update Posted: Feb 6, 2019
• Last Verified: Jan 1, 2019

• Additional relevant MeSH terms: Graft vs Host Disease

Study Results

Participant Flow

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Period Title: Overall Study
STARTED	20
COMPLETED	4
NOT COMPLETED	16

Baseline Characteristics

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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 Participants	20
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	53
Sex: Female, Male (Count of Participants)
Female	7 35%
Male	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 15%
Not Hispanic or Latino	17 85%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	1 5%
Black or African American	3 15%
White	16 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Primary Disease (Count of Participants)
Acute leukemia (ALL/AML)	12 60%
Chronic leukemia (CML/CLL)	4 20%
Lymphoma (NHL/HD)	2 10%
Myeloma	1 5%
Myeloproliferative neoplasm	1 5%

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events
Description	according to National Cancer Institute CTCAE, version 4.03
Time Frame	Up to 30 days following completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Serious Adverse Events	8 40%
Non-Serious Adverse Events	7 35%

2. Primary Outcome

Title	Probability of Treatment Failure at 6mo
Description	Kaplan-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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Number [probability of treatment failure]	0.4

3. Secondary Outcome

Title	Complete Response Rate
Description	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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Participants who could be evaluated for response (not missing data)

Arm/Group Title	Response Evaluated by MD	Response Evaluated by NIH
Arm/Group Description	Participants who receive carfilzomib	Participants who receive carfilzomib
Measure Participants	16	16
partial response	5 25%	4 NaN
mixed response	0 0%	4 NaN
unchanged	2 10%	1 NaN
progressive	2 10%	0 NaN
failed	7 35%	7 NaN

4. Secondary Outcome

Title	Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse
Description	The 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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Count of Participants [Participants]	7 35%

5. Secondary Outcome

Title	Probability of Failure-free Survival at 1 Year
Description	Kaplain-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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Number [probability of failure-free survival]	.32

6. Secondary Outcome

Title	Impact of Proteasome Inhibition
Description	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.
Time Frame	Up to 6 months

Outcome Measure Data

Analysis Population Description

Data were not collected because biologic studies were not performed. Response to study drug too minimal to justify time and expense.

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	0

7. Secondary Outcome

Title	Incidence of Discontinuation of All Systemic Immune-suppressive Therapies
Description	The incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Count of Participants [Participants]	2 10%

8. Secondary Outcome

Title	Overall Response Rate
Description	Overall 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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Physician impression ORR	4 20%
NIH ORR	3 15%

9. Secondary Outcome

Title	Probability of Overall Survival at 1 Year
Description	Kaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Number [probability of overall survival]	.65

10. Secondary Outcome

Title	Treatment Success
Description	Treatment 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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Number [participants]	0 0%

11. Secondary Outcome

Title	Use of Additional Systemic Immune-suppressive Therapies
Description	Addition of therapy after carfilzomib constitutes failure, could occur at any time from baseline to 12mo.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Number [participants]	13 65%

12. Secondary Outcome

Title	Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
Description	SF-36 subscales have min=0 and max=100; results given are actual scores at 12mo, with higher scores indicating higher quality of life.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
Norm-based physical functioning	36
norm-based role-physical score	33.6
norm-based bodily pain score	41.4
norm-based general health score	32.9
norm-based vitality score	42.7
norm-based social functioning	40.5
norm-based role-emotional score	40.3
norm-based mental health score	50
standardized physical component score	37
standardized mental component score	49

13. Secondary Outcome

Title	Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
Description	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)
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
physical well-being	21.5
social/family well-being	21.5
emotional well-being	18.5
functional well-being	16.5
BMT subscale	28
FACT-G	72.8
trial outcome index	65
FACT-BMT total	101.3

14. Secondary Outcome

Title	Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
Description	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.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
maximum activity score	66
adjusted activity score	57
modified adjusted activity score	60

15. Secondary Outcome

Title	Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
Description	Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

Only baseline surveys analyzed. Only 7 patients completed surveys at 6mo, not analyzed due to low number.

Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
Measure Participants	20
skin scale	32.5
energy scale	42.9
lung scale	5
eye scale	62.5
nutrition scale	5
psychological scale	25
mouth scale	0
overall summary score	21.6

Adverse Events

Time Frame	30 days after stopping study drug
Arm/Group Title	Treatment (Carfilzomib)
Arm/Group Description	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.
All Cause Mortality
	Treatment (Carfilzomib)
	Affected / at Risk (%)	# Events
Total	2/20 (10%)
Serious Adverse Events
	Treatment (Carfilzomib)
	Affected / at Risk (%)	# Events
Total	8/20 (40%)
Gastrointestinal disorders
nausea/vomitting/diarrhea	1/20 (5%)	1
General disorders
fever/infusion reaction	1/20 (5%)	1
Infections and infestations
sepsis	2/20 (10%)	2
Injury, poisoning and procedural complications
fall	1/20 (5%)	2
Renal and urinary disorders
acute renal failure/sepsis	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
pneumothorax	1/20 (5%)	1
hypoxia	1/20 (5%)	1
pneumonia	1/20 (5%)	1
respiratory failure	1/20 (5%)	1
Skin and subcutaneous tissue disorders
leg ulcers	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Carfilzomib)
	Affected / at Risk (%)	# Events
Total	7/20 (35%)
Blood and lymphatic system disorders
decreased lymphocyte count	2/20 (10%)	2
Gastrointestinal disorders
diarrhea	1/20 (5%)	1
esophageal varices	1/20 (5%)	1
Hepatobiliary disorders
increased ALT	1/20 (5%)	2
Infections and infestations
fungal lung infection	1/20 (5%)	1
rhinovirus	1/20 (5%)	1
Metabolism and nutrition disorders
hypokalemia	1/20 (5%)	1
intermittent hyperglycemia	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Left hip hemiarthroplasty	1/20 (5%)	1
myositis	1/20 (5%)	1
Skin and subcutaneous tissue disorders
bullous dermatitis	1/20 (5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.