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Chronic Graft Versus Host DiseasePhase 2NCT02491359

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

A Phase 2 study testing Carfilzomib, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Chronic Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Graft Versus Host Disease
What is being tested?
Carfilzomib, Laboratory Biomarker Analysis and Quality-of-Life Assessment
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
5 sitesUnited States
Study dates
12 Nov 2015to 12 Sep 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: Carfilzomib for Treatment of Chronic Graft vs. Host Disease

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.

Read the detailed description

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

  1. 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.

  1. 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.

Being tested
Carfilzomib, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called Kyprolis, PR-171

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT02491359
Study groupRoleWhat they receive
Treatment (carfilzomib)ExperimentalPatients 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.
Receives: Drug: Carfilzomib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Adverse Events

    according to National Cancer Institute CTCAE, version 4.03

    Measured: Up to 30 days following completion of study treatment

  2. 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.

    Measured: 6 months

Secondary outcomes (13)

  1. Complete Response Rate

    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.

    Measured: Up to 6 months

  2. Cumulative Incidence of Non-relapse Mortality and Primary Malignancy Relapse

    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.

    Measured: 1 year

  3. Probability of Failure-free Survival at 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.

    Measured: 1 year

  4. Impact of Proteasome Inhibition

    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.

    Measured: Up to 6 months

  5. Incidence of Discontinuation of All Systemic Immune-suppressive Therapies

    The incidence of complete discontinuation of all systemic immune-suppressive therapies will be determined at 1 year.

    Measured: 1 year

  6. Overall Response Rate

    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.

    Measured: 6 months

  7. Probability of Overall Survival at 1 Year

    Kaplan-Meier estimate assessed at 1 year for overall survival, defined as absence of death from any cause.

    Measured: 1 year

  8. Treatment Success

    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.

    Measured: 1 year

  9. Use of Additional Systemic Immune-suppressive Therapies

    Addition of therapy after carfilzomib constitutes failure, could occur at any time from baseline to 12mo.

    Measured: 1 year

  10. Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)

    SF-36 subscales have min=0 and max=100; results given are actual scores at 12mo, with higher scores indicating higher quality of life.

    Measured: baseline

  11. Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)

    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)

    Measured: baseline

  12. Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)

    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.

    Measured: baseline

  13. Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale

    Lee symptom scale (LSS) has subscales with min=0, max=100; results given are 12mo scores, with higher numbers indicating higher symptom burden.

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jul 2015 (estimated)
  2. Study start12 Nov 2015
  3. Primary completion19 Feb 2018
  4. Study completion12 Sep 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02491359
Sponsor's protocol ID
9228
Other IDs
NCI-2015-00809, 9228.00, 9228, P30CA015704
Status last verified
Jan 2019
First submitted
10 Jun 2015
Last updated
6 Feb 2019
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carfilzomib, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Chronic Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (time frame: Up to 30 days following completion of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02491359.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2019.

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