The Impact of Velcade(TM)on Antibody Secreting Cells in Sensitized Renal Allograft Candidates

NCT00722722 | Completed Phase 2 Results

• 1 other identifier: 08-000556
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Patients planning to have kidney transplantation who are sensitized to their donors have high levels of donor specific alloantibodies. High levels of donor specific antibodies put kidney transplant recipients at risk for rejection very early after transplant. This study is trying to determine if the drug bortezomib (Velcade ™) can reduce donor specific alloantibodies to a level that permits kidney transplantation without a high risk for rejection.

Conditions

Kidney Transplantation

Outcome Measures

Primary Outcomes (1)

• Response to Bortezomib Monotherapy

  Response to treatment with Bortezomib (BTZ) alone was defined as a reduction in serum Donor Specific Alloantibody (DSA) levels following treatment. DSA levels were measured prior to treatment and after treatment. A good response occurred if all DSA were reduced. A partial response when a reduction was observed in at least one DSA, but not all DSA. No response occurred when no reduction of any DSA was attained.

  6 months

Study Arms (3)

4 dose group

ACTIVE COMPARATOR

4 doses of bortezomib (1.3mg/m\^2 of body surface area)

Drug: Bortezomib

16 dose group

ACTIVE COMPARATOR

16 doses of bortezomib (1.3mg/m\^2 of body surface area)

Drug: Bortezomib

32 dose group

ACTIVE COMPARATOR

32 doses of bortezomib (1.3mg/m\^2 of body surface area)

Drug: Bortezomib

Interventions

Bortezomib DRUG

Velcade given in four-dose cycles intravenously (through a vein).

Also known as: Velcade(TM)

16 dose group; 32 dose group; 4 dose group

Eligibility Criteria

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

You may qualify if:

• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Female subject is post-menopausal, surgically sterilized, or she and/or sexual partner are willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
• Male subject agrees to use an acceptable method for contraception for the duration of the study.
• Renal transplant candidates who otherwise meet our acceptance criteria.
• Evidence of alloantibody in their serum (panel reactive antibody \>20% and specificities determined by single antigen flow bead assay).
• Sensitized patients with no living donors or have donor-specific antibody levels too high to undergo successful transplantation using our current protocols (T or B cell crossmatch channel shift \>500).

You may not qualify if:

• Patient has a platelet count of \<30 x 10\^9/L within 14 days before enrollment.
• Patient has an absolute neutrophil count (ANC) of \<1.0 x 10\^9/L within 14 days before enrollment.
• Patient has \>Grade 2 peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.
• Patient has hypersensitivity to bortezomib, boron or mannitol.
• Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
• Patient has received other investigational drugs within14 days before enrollment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for malignancy within 5 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Contraindication to kidney transplantation-active infection, comorbid medical conditions, etc.

Sponsors & Collaborators

• Mayo Clinic: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• Diwan TS, Raghavaiah S, Burns JM, Kremers WK, Gloor JM, Stegall MD. The impact of proteasome inhibition on alloantibody-producing plasma cells in vivo. Transplantation. 2011 Mar 15;91(5):536-41. doi: 10.1097/TP.0b013e3182081333.

  PMID: 21283064 BACKGROUND

• Moreno Gonzales MA, Gandhi MJ, Schinstock CA, Moore NA, Smith BH, Braaten NY, Stegall MD. 32 Doses of Bortezomib for Desensitization Is Not Well Tolerated and Is Associated With Only Modest Reductions in Anti-HLA Antibody. Transplantation. 2017 Jun;101(6):1222-1227. doi: 10.1097/TP.0000000000001330.

  PMID: 27379560 DERIVED

MeSH Terms

Interventions

Bortezomib

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Mark Stegall, MD
• Organization: Mayo Clinic

Stegall.Mark@mayo.edu

507-266-2812

Study Officials

• Mark D. Stegall, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: July 23, 2008
• First Posted: July 28, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: May 9, 2016
• Results First Posted: May 9, 2016

Record last verified: 2016-04

Locations

US (1)