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Chronic Graft Versus Host DiseasePhase 2NCT02513498

Ixazomib Citrate in Treating Patients With Chronic Graft-versus-Host Disease

A Phase 2 study testing Ixazomib Citrate, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Chronic Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 6 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 phase II trial studies how well ixazomib citrate 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?
Ixazomib Citrate, Laboratory Biomarker Analysis and Quality-of-Life Assessment
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
6 sitesUnited States
Study dates
8 Dec 2015to 27 Jun 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

  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
  • Agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
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  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
  • Agree to practice two effective contraception measures during the entire study treatment period and through 90 days after the last dose of study drug, OR
  • Agree to practice true abstinence or exclusively non-heterosexual activity when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception)
  • Patients must have a diagnosis of a chronic GVHD according to the National Institute of Health (NIH) Consensus Criteria
  • Patients must have failed at least one prior line of systemic immune suppressive therapy for management of chronic GVHD
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 75,000/mm^3; platelet transfusions are not allowed within 3 days before study enrollment
  • Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • Calculated creatinine clearance >= 30 mL/min

Who cannot join

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Major surgery within 14 days before 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 before study enrollment
  • Infection treated with appropriate antimicrobial therapy and without signs of progression/treatment failure does not constitute an exclusion criterion
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
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  • Chronic hypertension on medical therapy does not constitute an exclusion criterion
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
  • Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
  • Non-hematologic malignancy within the past 2 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
  • Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
  • Treatment with non-Food and Drug Administration (FDA) approved drug within 21 days of start of this trial
  • New systemic immune suppressive agent added for the treatment of chronic GVHD within 2 weeks prior to enrollment
  • Addition of a new systemic immune suppressive treatment simultaneously with ixazomib is also prohibited
  • Evidence of recurrent or progressive underlying malignant disease
  • Karnofsky performance status < 70%
  • Life expectancy less than 6 months

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

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

This phase II trial studies how well ixazomib citrate 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. Ixazomib citrate may be an effective treatment for chronic graft-versus-host disease.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the proportion of subjects with treatment failure by 6 months of ixazomib (ixazomib citrate) treatment 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-suppressive therapy 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)], Human Activity Profile [HAP]) at study enrollment, 6 months, and 1 year.

  1. Study biologic effects of proteasome inhibition.

OUTLINE:

Patients receive ixazomib citrate orally (PO) once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.

After completion of study treatment, patients are followed up for 6 months.

Being tested
Ixazomib Citrate, 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.

  • Ixazomib CitrateDrug

    Also called MLN-9708, MLN9708, Ninlaro

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT02513498
Study groupRoleWhat they receive
Treatment (ixazomib citrate)ExperimentalPatients receive ixazomib citrate PO once weekly on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive an additional 6 courses of ixazomib citrate.
Receives: Drug: Ixazomib Citrate; 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 Common Terminology Criteria for Adverse Events, version 4.0

    Measured: Up to 30 days following completion of study treatment

  2. Probability of Treatment Failure at 6 Months

    Kaplan-Meier estimate assessed at 6 months for probability of treatment failure, defined as addition of a line of systemic immune-suppressive therapy, recurrent malignancy, or death.

    Measured: 6 months

Secondary outcomes (14)

  1. Biologic Studies

    The biologic impact of proteasome inhibition in the treatment of chronic GVHD will be assessed.

    Measured: Up to 6 months

  2. Complete Response (CR) Rate

    Response will be determined by both clinician-defined, as well as separately calculated according to the proposed response definitions of the NIH Consensus Conference.

    Measured: 6 months

  3. Probability of Non-relapse Mortality at 1 Year

    Kaplan-Meier estimate assessed at 1 year for probability of non-relapse mortality, defined as death in the absence of primary malignancy relapse after transplant.

    Measured: 1 year

  4. Cumulative Incidence of Primary Malignancy 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.

    Measured: 1 year

  5. Probability of Failure-free Survival at 1 Year

    Kaplan-Meier estimate assessed at 1 year for failure-free survival, defined as the absence of death from any cause, relapse or addition of secondary immune suppressive agents.

    Measured: 1 year

  6. 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

  7. Overall Response Rate (ORR) (Complete Response + Partial Response)

    ORR 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

  8. 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

  9. Treatment Success

    Treatment success will be estimated at 1 year with a composite outcome of complete resolution of all reversible chronic graft-versus-host disease (GVHD) manifestations, discontinuation of all systemic immune suppressive agents, and freedom from death or primary malignancy relapse after transplant.

    Measured: 1 year

  10. Use of Additional Systemic Immune Suppressive Therapies

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

    Measured: 1 year

  11. 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: 1 year

  12. 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: 1 year

  13. 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: 1 year

  14. 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: 1 year

Timeline

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

  1. First posted31 Jul 2015 (estimated)
  2. Study start8 Dec 2015
  3. Primary completion5 Jan 2018
  4. Study completion27 Jun 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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02513498
Sponsor's protocol ID
9292
Other IDs
NCI-2015-00882, X16032, 9292, P30CA015704
Status last verified
Jan 2019
First submitted
29 Jul 2015
Last updated
6 Feb 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ixazomib Citrate, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Chronic Graft Versus Host Disease, run by Fred Hutchinson Cancer Center at 6 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 16 inclusion and 23 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 6 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 NCT02513498.

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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