Clinical trial NCT02513498: Ixazomib Citrate in Treating Patients With Chronic Graft-versus-Host Disease
Official title: Ixazomib for Treatment of Chronic Graft vs. Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Graft Versus Host Disease
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-07-31
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: Up to 30 days following completion of study treatment
measure: Probability of Treatment Failure at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Biologic Studies
timeFrame: Up to 6 months
measure: Complete Response (CR) Rate
timeFrame: 6 months
measure: Probability of Non-relapse Mortality at 1 Year
timeFrame: 1 year
measure: Cumulative Incidence of Primary Malignancy Relapse
timeFrame: 1 year
measure: Probability of Failure-free Survival at 1 Year
timeFrame: 1 year
measure: Incidence of Discontinuation of All Systemic Immune Suppressive Therapies
timeFrame: 1 year
measure: Overall Response Rate (ORR) (Complete Response + Partial Response)
timeFrame: 6 months
measure: Probability of Overall Survival at 1 Year
timeFrame: 1 year
measure: Treatment Success
timeFrame: 1 year
measure: Use of Additional Systemic Immune Suppressive Therapies
timeFrame: 1 year
measure: Symptoms as Measured by Patient Self-report--Short Form-36 (SF-36)
timeFrame: 1 year
measure: Symptoms as Measured by Patient Self-report--Functional Assessment of Chronic Illness Therapy (FACT)
timeFrame: 1 year
measure: Symptoms as Measured by Patient Self-report--Human Activities Profile (HAP)
timeFrame: 1 year
measure: Symptoms as Measured by Patient Self-report--Lee Chronic GVHD Symptom Scale
timeFrame: 1 year
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Stephanie Lee
role: PRINCIPAL_INVESTIGATOR
References: