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Trial record 42 of 184 for:    carfilzomib OR pr-171

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
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

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:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
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 : November 12, 2015
Actual Primary Completion Date : February 19, 2018
Actual Study Completion Date : September 12, 2018


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 Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Incidence of Adverse Events [ Time Frame: 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 [ 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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)


  12. 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.


  13. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
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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
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephanie Lee Fred Hutch/University of Washington Cancer Consortium
  Study Documents (Full-Text)

Documents provided by Fred Hutchinson Cancer Research Center:

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Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02491359     History of Changes
Other Study ID Numbers: 9228
NCI-2015-00809 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9228.00
9228 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Posted: July 8, 2015    Key Record Dates
Results First Posted: February 6, 2019
Last Update Posted: February 6, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases