B-Cell Targeted Carfilzomib Desensitization

NCT02442648 | Unknown Phase 1 DMC

• 1 other identifier: Carfilzomib
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

The primary purpose of this study is to provide a preliminary evaluation of the safety and potential efficacy of carfilzomib in reducing HLA antibody levels in highly sensitized kidney transplant candidates.

Conditions

Transplants and Implants

Keywords

Renal Transplantation; Carfilzomib; Kyprolis; Desensitization

Outcome Measures

Primary Outcomes (1)

• Safety of carfilzomib will be assessed by incidence of grade 3 and above non-hematologic toxicities, incidence of grade 4 hematologic toxicities and incidence of all grades of peripheral neuropathy

  The primary objective of the proposed study is to evaluate the safety of carfilzomib alone and in combination with plasmapheresis, with or without rituximab, for desensitization in highly sensitized kidney transplant candidates. Safety will be assessed by overall safety of carfilzomib when used in the desensitization setting, incidence of grade 3 and above non-hematologic toxicities, incidence of grade 4 hematologic toxicities and incidence of all grades of peripheral neuropathy.

  6 months

Secondary Outcomes (1)

• Efficacy of carfilzomib

  6 months

Study Arms (4)

Group A (5-8 patients) - Carfilzomib

EXPERIMENTAL

Two cycles of carfilzomib desensitization given.

Drug: Carfilzomib

Group B (5-8 patients) - Carfilzomib/plasmapheresis

EXPERIMENTAL

Two cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy

Drug: Carfilzomib

Group C (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis

EXPERIMENTAL

1 dose of rituximab prior to two cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy

Drug: Carfilzomib; Drug: Rituximab

Group D (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis

EXPERIMENTAL

1 dose of rituximab prior to three cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy

Drug: Carfilzomib; Drug: Rituximab

Interventions

Carfilzomib DRUG

Carfilzomib will be administered for desensitization per study protocol.

Also known as: Krypolis

Group A (5-8 patients) - Carfilzomib; Group B (5-8 patients) - Carfilzomib/plasmapheresis; Group C (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis; Group D (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis

Rituximab DRUG

Rituximab will be administered for desensitization per study protocol.

Also known as: Rituxan

Group C (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis; Group D (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis

Eligibility Criteria

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

You may qualify if:

• Patient is between 18 and 65 years of age, inclusive.
• Voluntary written informed consent.
• Female subject is either postmenopausal for at least 1 year prior to initiation of study treatment, is surgically sterilized, or if of childbearing potential, agrees to practice 2 effective methods of contraception through 3 months after the last dose of carfilzomib.
• Male subjects, even if surgically sterilized (i.e. status post-vasectomy) must agree to 1 effective contraception.
• Patient with eligible living donor will have: 1) positive cytotoxic crossmatch, or 2) moderate to strongly positive T or B cell flow cytometry crossmatch (with confirmed donor-specific antibodies (DSAs) on solid-phase assay at screening, or 3) \> 2 low to moderate level DSAs (DSA value from 1500 - 8000 MFI).
• LVEF ≥ 45% within 3 months of evaluation.
• Patient that is on the kidney transplant waiting list awaiting a deceased donor transplant and has a current or peak cytotoxic or calculated panel reactive antibody (PRA) \> 30%.
• Patient must have no known contraindications to treatment with carfilzomib or rituximab.
• Review of pre-transplant medical clearance by the patient's dialysis nephrologist or transplant nephrologist or treating physician to assure the patient is medically acceptable for study entry.
• Patient must be vaccinated against hepatitis B virus.

You may not qualify if:

• Patient has significant neuropathy (Grades 3 - 4, or Grade 2 with pain) by CTCAE criteria within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has ADQI Heart Failure in ESRD Classification System Class 2NR or greater (Appendix B), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient has received other investigational drugs within 14 days prior to initiation of study treatment.
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of: 1) complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, 2) an in situ malignancy, 3) low-risk prostate cancer after curative therapy, or 4) any cancer with a cure rate ≥ 99%.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
• Patients with a hemoglobin count \<8 g/dL (80 g/L) (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines), absolute neutrophil count \< 1,000/mm3 or platelet count \< 75,000/mm3 within 14 days of consent.
• Patients who are anti-HIV-positive, or HBsAg-positive, or anti-HCV positive with a detectable HCV viral load on testing performed within one year of consent.
• Patients with current or recent severe systemic infections requiring treatment (systemic antibiotics, antivirals, or antifungals) within the 2 weeks prior to initiation of study treatment.
• Receipt of a live vaccine within 4 weeks prior to initiation of study treatment.
• Evidence of severe liver disease by medical history or physical exam with abnormal liver profile (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] or total bilirubin \> 1.5 times upper limit of normal \[ULN\]) on testing performed within 30 days of consent.
• Female subject is pregnant or breast-feeding.
• Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
• Patient is not yet on dialysis.

Sponsors & Collaborators

• E. Steve Woodle: lead
• Amgen: collaborator

Study Sites (2)

The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45267, United States

RECRUITING

MeSH Terms

Interventions

carfilzomib; Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• E. Steve Woodle, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Central Study Contacts

E. Steve Woodle, MD

CONTACT

513-558-6001; woodlees@uc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Solid Organ Transplantation

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: May 13, 2015
• Study Start: December 1, 2014
• Primary Completion: June 1, 2021
• Study Completion: September 1, 2021
• Last Updated: June 30, 2020

Record last verified: 2020-06

Locations

US (2)