Phase 2 N=20 Treatment

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

Chronic Graft Versus Host Disease

Bottom Line

View on ClinicalTrials.gov: NCT02491359 ↗

Enrolled (actual)

Serious AEs

40.0%

Results posted

Feb 2019

Primary outcome: Primary: Incidence of Adverse Events — 8; 7 participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Carfilzomib (Drug); Laboratory Biomarker Analysis (Other); Quality-of-Life Assessment (Other); Questionnaire Administration (Other)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Fred Hutchinson Cancer Center
Primary completion: Feb 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Incidence of Adverse Events	8; 7	—
PRIMARY Probability of Treatment Failure at 6mo	0.4	—
SECONDARY Complete Response Rate	5; 4; 0; 4; 2; 1	—
SECONDARY Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse	7	—
SECONDARY Probability of Failure-free Survival at 1 Year	.32	—
SECONDARY Impact of Proteasome Inhibition	—	—
SECONDARY Incidence of Discontinuation of All Systemic Immune-suppressive Therapies	2	—
SECONDARY Overall Response Rate	4; 3	—
SECONDARY Probability of Overall Survival at 1 Year	.65	—
SECONDARY Treatment Success	—	—
SECONDARY Use of Additional Systemic Immune-suppressive Therapies	13	—
SECONDARY Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)	36; 33.6; 41.4; 32.9; 42.7; 40.5	—
SECONDARY Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)	21.5; 21.5; 18.5; 16.5; 28; 72.8	—
SECONDARY Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)	66; 57; 60	—
SECONDARY Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale	32.5; 42.9; 5; 62.5; 5; 25	—

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.

Eligibility Criteria

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) = = 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) 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02491359). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.