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

NCT02491359 | Completed Phase 2 Results DMC

• 4 other identifiers: 9228NCI-2015-008099228.00P30CA015704
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

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.

Conditions

Chronic Graft Versus Host Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  according to National Cancer Institute CTCAE, version 4.03

  Up to 30 days following completion of study treatment

• Probability of Treatment Failure at 6mo

  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.

  6 months

Secondary Outcomes (13)

• Complete Response Rate

  Up to 6 months

• Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse

  1 year

• Probability of Failure-free Survival at 1 Year

  1 year

• Impact of Proteasome Inhibition

  Up to 6 months

• Incidence of Discontinuation of All Systemic Immune-suppressive Therapies

  1 year

Study Arms (1)

Treatment (carfilzomib)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Carfilzomib DRUG

Given IV

Also known as: Kyprolis, PR-171

Treatment (carfilzomib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (carfilzomib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (carfilzomib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (carfilzomib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

carfilzomib

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Dr. Joseph Pidala
• Organization: H. Lee Moffitt Cancer Center

joseph.pidala@moffitt.org

813-745-2556

Study Officials

• Stephanie Lee

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: July 8, 2015
• Study Start: November 12, 2015
• Primary Completion: February 19, 2018
• Study Completion: September 12, 2018
• Last Updated: February 6, 2019
• Results First Posted: February 6, 2019

Record last verified: 2019-01

Locations

US (5)