Ixazomib for Desensitization

NCT03213158 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 2017-0429A534280SMPH\MEDICINE\NEPHROLOGYProtocol ver 3June 2019
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to find out how well ixazomib (the study drug) works to desensitize highly sensitized kidney transplant recipients.

Conditions

Kidney Diseases; End Stage Renal Disease

Outcome Measures

Primary Outcomes (2)

• Efficacy of Ixazomib: Percentage of Participants With > 20 Percent Decline in Calculated Panel Reactive Antibody (cPRA)

  up to 12 months

• Efficacy of Ixazomib: Percentage of Participants Received Successful Kidney Transplantation Within 12 Months

  up to 12 months

Secondary Outcomes (7)

• Safety of Ixazomib as Assesses by Percentage of Participants With Cardiovascular Complications Within 12 Months

  up to 12 months

• Safety of Ixazomib as Assesses by Percentage of Participants With Hematological Complications Within 12 Months

  up to 12 months

• Safety of Ixazomib as Assesses by Percentage of Participants With Malignancies Within 12 Months

  up to 12 months

• Safety of Ixazomib as Assesses by Percentage of Participants With Gastrointestinal Symptoms Within 12 Months

  up to 12 months

• Safety of Ixazomib as Assesses by Percentage of Participants Caught Infection Within 12 Months

  up to 12 months

Other Outcomes (2)

• Change in Circulating BAFF Levels as Assessed by BAFF ELISA Assay

  Baseline, 3 months

• Change in Circulating APRIL Levels as Assessed by APRIL ELISA Assay

  Baseline, 3 months

Study Arms (1)

Highly sensitized kidney transplant candidates

EXPERIMENTAL

The study population will include all highly sensitized kidney transplant candidates on the waitlist for more than 24 months at University of Wisconsin.

Drug: Ixazomib Oral Capsule

Interventions

Ixazomib Oral Capsule DRUG

Highly sensitized kidney transplant candidates on the waitlist for more than 24 months will receive ixazomib 3 mg (and dexamethasone 20 mg) on days 1, 8, and 15 of a 28 cycle. Patients will take ixazomib and dexamethasone for twelve (12) 28-day cycles.

Highly sensitized kidney transplant candidates

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 18-70 years of age.
• Able to provide informed consent.
• 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 30 days after the last dose of study drug, OR agree to practice true abstinence 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 effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, or Agree to practice true abstinence 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 be highly sensitized with a cPRA ≥ 80%
• Be active on the waitlist for kidney transplantation \> 24 months to confirm their inability to receive a deceased donor transplant because of their sensitization status.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
• Hemoglobin higher than 6 g/dL
• 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 requiring hospitalization within 6 months before enrollment
• Infection requiring systemic antibiotic therapy or other serious 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 CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Inability to take oral medication
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Grade 2 or greater peripheral neuropathy according to NCI Common Terminology Criteria for Adverse Events (CTCAE)
• Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 6 months of the start of this trial and throughout the duration of this trial
• Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not
• Active or treated infection for HIV, HCV or HBV
• History of Liver cirrhosis, biopsy confirmed
• Elevated transaminases (greater than 3 times the upper limit of normal)
• Known hypersensitivity to ixazomib

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Wilson N, Reese S, Ptak L, Aziz F, Parajuli S, Jucaud V, Denham S, Mishra A, Cascalho M, Platt JL, Hematti P, Djamali A. Ixazomib for Desensitization (IXADES) in Highly Sensitized Kidney Transplant Candidates: A Phase II Clinical Trial. Kidney360. 2023 Jun 1;4(6):e796-e808. doi: 10.34067/KID.0000000000000113. Epub 2023 Mar 23.

  PMID: 36951387 DERIVED

MeSH Terms

Conditions

Kidney Diseases; Kidney Failure, Chronic

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Fahid Aziz, MD
• Organization: University of Wisconsin - Madison

faziz@wisc.edu

(608) 262-5420

Study Officials

• Arjang Djamali, MD, MS, FASN

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: April 26, 2017
• First Posted: July 11, 2017
• Study Start: September 15, 2017
• Primary Completion: April 16, 2021
• Study Completion: April 16, 2021
• Last Updated: June 1, 2022
• Results First Posted: May 11, 2022

Record last verified: 2022-05

Locations

US (1)