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

NCT ID: NCT02513498

Last Updated: 2019-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-08
• Study Completion Date: 2018-06-27

Brief 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 tissue. Ixazomib citrate may be an effective treatment for chronic graft-versus-host disease.

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

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-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.

V. 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.

Conditions

Chronic Graft Versus Host Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (ixazomib citrate)

Patients 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.

Group Type: EXPERIMENTAL

Ixazomib Citrate

Intervention Type: DRUG

Given PO

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

Ixazomib Citrate

Given PO

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

MLN-9708; MLN9708; Ninlaro; Quality of Life Assessment

Eligibility Criteria

Inclusion Criteria

• 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)
• 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

Exclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie Lee

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-00882

Identifier Type: REGISTRY

Identifier Source: secondary_id

X16032

Identifier Type: -

Identifier Source: secondary_id

9292

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9292

Identifier Type: -

Identifier Source: org_study_id