Carfilzomib in Treating Patients With Chronic Graft-Versus-Host Disease
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|ClinicalTrials.gov Identifier: NCT02491359|
Recruitment Status : Completed
First Posted : July 8, 2015
Results First Posted : February 6, 2019
Last Update Posted : February 6, 2019
|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|
I. Determine proportion of subjects with treatment failure by 6 months of carfilzomib therapy for chronic graft-versus-host disease (GVHD).
I. Determine 3 month overall (complete + partial), and complete response rate.
II. Determine 6 month overall (complete + partial), and complete response rate.
III. 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.
IV. 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.
V. Study biologic effects of proteasome inhibition.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Carfilzomib for Treatment of Chronic Graft vs. Host Disease|
|Actual Study Start Date :||November 12, 2015|
|Actual Primary Completion Date :||February 19, 2018|
|Actual Study Completion Date :||September 12, 2018|
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.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Incidence of Adverse Events [ Time Frame: Up to 30 days following completion of study treatment ]according to National Cancer Institute CTCAE, version 4.03
- Probability of Treatment Failure at 6mo [ Time Frame: 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.
- Complete Response Rate [ Time Frame: 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.
- Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse [ Time Frame: 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.
- Probability of Failure-free Survival at 1 Year [ Time Frame: 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.
- Impact of Proteasome Inhibition [ Time Frame: 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.
- Incidence of Discontinuation of All Systemic Immune-suppressive Therapies [ Time Frame: 1 year ]The incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year.
- Overall Response Rate [ Time Frame: 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.
- Probability of Overall Survival at 1 Year [ Time Frame: 1 year ]Kaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause.
- Treatment Success [ Time Frame: 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.
- Use of Additional Systemic Immune-suppressive Therapies [ Time Frame: 1 year ]Addition of therapy after carfilzomib constitutes failure, could occur at any time from baseline to 12mo.
- Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36) [ Time Frame: 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.
- Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT) [ Time Frame: 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)
- Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP) [ Time Frame: 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.
- Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale [ Time Frame: baseline ]Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02491359
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Stephanie Lee||Fred Hutch/University of Washington Cancer Consortium|