Transplants and ImplantsPhase 1NCT02442648
B-Cell Targeted Carfilzomib Desensitization
A Phase 1 study testing Carfilzomib and Rituximab in people with Transplants and Implants, run by E. Steve Woodle at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Transplants and Implants
- What is being tested?
- Carfilzomib and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2014to Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
The Christ Hospital
Cincinnati, Ohio, 45219
E. Steve Woodle, MD, 513-558-6001, Woodlees@uc.edu
E. Steve Woodle, MD
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
E. Steve Woodle, MD, 513-558-6001, Woodlees@uc.edu
E. Steve Woodle, MD
About this study
Official title: B-Cell Targeted Desensitization With Carfilzomib for Preformed Anti-HLA Antibodies in Patients Awaiting Kidney Transplantation
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.
Read the detailed description
This study is a non-randomized, open label, iterative pilot study. The duration of study will include a 16 month enrollment period and 5 to 6 months of follow-up. A total of 32 patients, male and female, between the ages 18 to 65 will be enrolled.
- Conditions
- Transplants and Implants
- Being tested
- Carfilzomib, Rituximab
- Keywords
- Renal Transplantation, Carfilzomib, Kyprolis, Desensitization
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Krypolis
Carfilzomib will be administered for desensitization per study protocol.
RituximabDrug
Also called Rituxan
Rituximab will be administered for desensitization per study protocol.
| Study group | Role | What they receive |
|---|---|---|
| Group A (5-8 patients) - Carfilzomib | Experimental | Two cycles of carfilzomib desensitization given. Receives: Drug: Carfilzomib |
| Group B (5-8 patients) - Carfilzomib/plasmapheresis | Experimental | Two cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy Receives: 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 Receives: 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 Receives: Drug: Carfilzomib; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
Efficacy of carfilzomib
The primary objective of the proposed study is to evaluate the efficacy of carfilzomib alone and in combination with plasmapheresis, with or without rituximab, for desensitization in highly sensitized kidney transplant candidates. Efficacy will be measured by percent reduction in immunodominant DSA (iDSA) [highest titer DSA (MFI)] and/or immunodominant antibody (iAb) from pre-treatment to 48 hours after the last plasmapheresis treatment.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startDec 2014
- Primary completionJun 2021 (estimated)
- Study completionSep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transplants and ImplantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- E. Steve Woodle
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, E. Steve Woodle, University of Cincinnati
- Investigators
- E. Steve Woodle, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442648
- Sponsor's protocol ID
- Carfilzomib
- Status last verified
- Jun 2020
- First submitted
- 4 Mar 2015
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- B-Cell Targeted Desensitization With Carfilzomib for Preformed Anti-HLA Antibodies in Patients Awaiting Kidney Transplantation
- ClinicalTrials.gov ID
- NCT02442648
- Acronym / sponsor ID
- Carfilzomib
- Conditions
- Transplants and Implants
- Keywords
- Renal Transplantation, Carfilzomib, Kyprolis, Desensitization
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- E. Steve WoodleUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Dec 2014
- Primary completion
- Jun 2021 (estimated)
- Study completion
- Sep 2021 (estimated)
- First posted
- 13 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a non-randomized, open label, iterative pilot study. The duration of study will include a 16 month enrollment period and 5 to 6 months of follow-up. A total of 32 patients, male and female, between the ages 18 to 65 will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A (5-8 patients) - Carfilzomib | Experimental | Drug: CarfilzomibTwo cycles of carfilzomib desensitization given. |
| Group B (5-8 patients) - Carfilzomib/plasmapheresis | Experimental | Drug: CarfilzomibTwo cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy |
| Group C (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis | Experimental | Drug: Carfilzomib, Drug: Rituximab1 dose of rituximab prior to two cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy |
| Group D (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis | Experimental | Drug: Carfilzomib, Drug: Rituximab1 dose of rituximab prior to three cycles of carfilzomib desensitization given with weekly plasmapheresis prior to carfilzomib therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (15 listed)
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarfilzomibAlso: KrypolisCarfilzomib will be administered for desensitization per study protocol. | Drug | 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 |
| RituximabAlso: RituxanRituximab will be administered for desensitization per study protocol. | Drug | Group C (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis, Group D (5-8 patients) - Rituximab/Carfilzomib/plasmapheresis |
Primary outcome
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
Time frame: 6 months
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.
1 secondary outcome
Efficacy of carfilzomib
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E. Steve Woodle, MD principal investigator
University of Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carfilzomib and Rituximab in people with Transplants and Implants, run by E. Steve Woodle at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact E. Steve Woodle, MD (513-558-6001, woodlees@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2020.