Clinical trial NCT02491359: Carfilzomib in Treating Patients With Chronic Graft-Versus-Host Disease
Official title: Carfilzomib for Treatment of Chronic Graft vs. Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Graft Versus Host Disease
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-07-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

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.

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.

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) =\< 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

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: Up to 30 days following completion of study treatment
measure: Probability of Treatment Failure at 6mo
timeFrame: 6 months
Secondary outcomes:
measure: Complete Response Rate
timeFrame: Up to 6 months
measure: Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse
timeFrame: 1 year
measure: Probability of Failure-free Survival at 1 Year
timeFrame: 1 year
measure: Impact of Proteasome Inhibition
timeFrame: Up to 6 months
measure: Incidence of Discontinuation of All Systemic Immune-suppressive Therapies
timeFrame: 1 year
measure: Overall Response Rate
timeFrame: 6 months
measure: Probability of Overall Survival at 1 Year
timeFrame: 1 year
measure: Treatment Success
timeFrame: 1 year
measure: Use of Additional Systemic Immune-suppressive Therapies
timeFrame: 1 year
measure: Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
timeFrame: baseline
measure: Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
timeFrame: baseline
measure: Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
timeFrame: baseline
measure: Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
timeFrame: baseline
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute (UPCI)
state: Pennsylvania
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Stephanie Lee
role: PRINCIPAL_INVESTIGATOR
References: