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

NCT02513498 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 9292NCI-2015-00882X16032P30CA015704
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 6

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.

Conditions

Chronic Graft Versus Host Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse Events

  According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0

  Up to 30 days following completion of study treatment

• 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.

  6 months

Secondary Outcomes (14)

• Biologic Studies

  Up to 6 months

• Complete Response (CR) Rate

  6 months

• Probability of Non-relapse Mortality at 1 Year

  1 year

• Cumulative Incidence of Primary Malignancy Relapse

  1 year

• Probability of Failure-free Survival at 1 Year

  1 year

Study Arms (1)

Treatment (ixazomib citrate)

EXPERIMENTAL

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.

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

Interventions

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ixazomib citrate)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ixazomib citrate)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

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

Study Sites (6)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome

Interventions

ixazomib

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: July 29, 2015
• First Posted: July 31, 2015
• Study Start: December 8, 2015
• Primary Completion: January 5, 2018
• Study Completion: June 27, 2018
• Last Updated: February 6, 2019
• Results First Posted: February 6, 2019

Record last verified: 2019-01

Locations

US (6)