Quantitating the Impact of Plerixafor

• Status: Recruiting
• Trial end date: 2020-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to conduct a proof of concept pilot study that will provide a preliminary evaluation of the safety of plerixafor alone or in combination with bortezomib on plasma cell mobilization, Human Leukocyte Antigen (HLA) antibody levels and toxicity profile in sensitized patients awaiting kidney transplantation.

The secondary objective of this study is to conduct additional analyses of the study regimen on HLA antibody levels using multiple different assays and statistical analysis.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: E. Steve Woodle
• Collaborator: Sanofi-Synthelabo
• Treatments: Bortezomib; JM 3100; Plerixafor

Criteria

Inclusion Criteria:

1. Male and female patients between 18 and 65 years of age (inclusive) with end-stage renal disease awaiting kidney transplantation.

2. Patient with eligible living donor will have: donor specific antibody (DSA) against living donor of >5,000 mean fluorescence intensity (MFI) or a positive T or B cell flow cytometry crossmatch.

3. Patient that is on the kidney transplant waiting list awaiting a deceased donor transplant and has an immunodominant antibody (iAb) of >8,000MFI or has a current or peak calculated panel reactive antibody (cPRA) >20%.

4. 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

5. 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 from the time of signing the informed consent form through 3 months after the last dose of plerixafor and/or bortezomib, or agrees to completely abstain from heterosexual intercourse. Women of childbearing potential must have a negative serum pregnancy test within the last 48 hours prior to receiving study medication.

6. Male subjects, even if surgically sterilized (i.e. status post-vasectomy) must agree to 1 of the following effective contraception through 3 months after end of study.

7. Review of pre-transplant medical clearance by the patient's transplant nephrologist to assure the patient is medically acceptable for study entry.

8. Cardiac evaluation by transplant nephrologist with clearance documented in writing to participate in the study.

Exclusion Criteria:

1. Known hypersensitivity to bortezomib, boron or mannitol, plerixafor or any of its components.

2. Actual body weight exceeds 175% of ideal body mass.

3. Subjects judged by the investigator to be at significant risk of failing to comply with the requirements of the protocol or unable to cooperate or communicate with the investigator.

4. Abnormal electrocardiogram (ECG) with clinically significant ventricular arrhythmias or other conduction abnormality that in the opinion of the investigator warrants exclusion of the subject from the trial.

5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix A), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

6. Patient has Grade 2 peripheral neuropathy by Common Toxicity Criteria for Adverse Effects (CTCAE) criteria within 14 days before enrollment.

7. Patients with an absolute neutrophil count < 1,000/mm3 or platelet count < 75,000/mm3 within 30 days of consent.

8. Patient has received other investigational drugs within 14 days prior to initiation of study treatment.

9. Receipt of a live vaccine within 4 weeks prior to initiation of study treatment.

10. Received blood transfusions within 30 days prior to trial entry.

11. Serious medical (other than renal disease) or psychiatric illness likely to interfere with participation in this clinical study.

12. Patients who are anti-HIV-positive, anti-Hepatitis C Virus (HCV) positive with a detectable viral load, or HBsAg-positive on testing performed within one year of consent.

13. History of malignancy within the past 5 years that is not considered to be cured, with the exception of localized basal cell carcinoma of the skin (excised ≥ 2 years prior to randomization).

14. Evidence of severe liver disease 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.

15. Patients with current or severe systemic infections.

16. Pregnant or nursing (lactating) women and women who might become pregnant during the study.