Carfilzomib + Belatacept for Kidney Transplant Rejection

(CarBel Trial)

Recruiting at 11 trial locations

Overseen By Yvonne Morrison, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Steroids, Immunosuppressants

Must not be taking: Experimental drugs

Disqualifiers: Cancer, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, carfilzomib (a proteasome inhibitor) and belatacept (an immunosuppressant), to determine if they can better protect transplanted kidneys by reducing harmful antibodies and inflammation. Researchers aim to discover if these drugs, when added to standard treatments, can improve kidney function for those experiencing specific types of kidney transplant rejection. Individuals who have had a kidney transplant and are dealing with rejection issues may find this trial suitable, provided their kidney function is above a certain level and they meet other health criteria. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants, offering a chance to contribute to important advancements in kidney transplant care.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, it mentions that the study drugs are added to the usual immunosuppression treatment, suggesting you may continue your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that carfilzomib, also known as Kyprolis®, has undergone safety testing in various conditions, including relapsed multiple myeloma. In these studies, about 11% of patients experienced kidney problems, such as renal insufficiency and acute renal failure, highlighting the need to monitor kidney function during treatment.

Belatacept, marketed as Nulojix®, is used in kidney transplant patients to prevent organ rejection. Some studies have found that patients taking belatacept might face a higher risk of infections, including a serious brain infection called PML (progressive multifocal leukoencephalopathy). However, it is generally considered a safer option compared to other immunosuppressive drugs.

Both drugs have received FDA approval for different uses, indicating a reasonable safety profile. Nonetheless, regular check-ups and communication with healthcare providers are essential to manage any potential side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine Carfilzomib and Belatacept, offering a unique approach to tackling kidney transplant rejection. Unlike standard treatments that primarily focus on general immunosuppression, Carfilzomib, a proteasome inhibitor, targets specific pathways involved in immune cell function, potentially reducing rejection more effectively. Belatacept, on the other hand, selectively blocks T-cell activation, which is crucial in preventing the immune system from attacking the transplanted kidney. This combination could provide a more targeted and potentially less toxic alternative to conventional treatments, which often rely on broad immunosuppressive drugs like Tacrolimus and Mycophenolate.

What evidence suggests that carfilzomib and belatacept could be effective for kidney transplant rejection?

Research has shown that belatacept in kidney transplants can reduce the risk of death by up to 45% over seven years. It proves effective, with about 8% to 12% of patients experiencing acute rejection in the first year. Carfilzomib has shown promise in treating antibody-mediated rejection (AMR) in kidney transplants, particularly in early cases. In this trial, participants in the investigational treatment arm will receive a combination of belatacept and carfilzomib. Studies indicate that this combination can greatly improve kidney survival by lowering harmful antibodies. This approach aims to enhance kidney function and increase the long-term success of transplants. ^{6 7 8 9 10}

Who Is on the Research Team?

Scott Sanoff, MD, Ph.D.

Principal Investigator

Duke University Medical Center: Transplantation

Stuart J Knechtle, M.D.

Principal Investigator

Duke University Medical Center: Transplantation

Are You a Good Fit for This Trial?

This trial is for kidney transplant patients experiencing rejection more than 6 months post-transplant or persistent ABMR less than 6 months after. Participants must be on standard immunosuppression and steroids but still have active chronic ABMR.

Inclusion Criteria

I have a specific type of kidney transplant rejection.

I understand the study and agree to participate.

I recovered from COVID-19 more than 21 days ago.

Exclusion Criteria

Serious medical or mental health issues that could interfere with the study

I was diagnosed or treated for cancer, excluding certain skin cancers, in the last 2 years.

Very low blood counts (hemoglobin, neutrophils, or platelets)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carfilzomib and belatacept therapy along with steroids and maintenance immunosuppression

3 months

Monthly visits (in-person)

Extended Treatment

Participants continue receiving belatacept, mycophenolate, prednisone, and tacrolimus

3 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept
• Carfilzomib

Trial Overview The study tests the safety and effectiveness of combining Carfilzomib with Belatacept, alongside usual immunosuppressants, to improve kidney function by reducing antibodies against the transplanted organ and affecting immune response.

How Is the Trial Designed?

Group I: Investigational Treatment Arm Experimental Treatment 2 Interventions

Study Entry to Month-3 participants will receive: * Steroid pulse/taper * Kyprolis® (Carfilzomib) * Nulojix® (Belatacept) * Tacrolimus * Mycophenolate * Prednisone After 3 months participants will receive: * Belatacept + * Mycophenolate * Prednisone * Tacrolimus

Group II: Conventional Treatment Arm Experimental Treatment 2 Interventions

Study Entry to Month-3 participants will receive: * Steroid pulse/taper * Intravenous Immunoglobulin (IVIG) * Tacrolimus OR Belatacept + * Mycophenolate * Prednisone After 3 months participants will receive: * Kyprolis® (Carfilzomib) * Nulojix ® (Belatacept) * Tacrolimus * Mycophenolate * Prednisone After an additional 3 months (6 months from study entry) participants will receive: * Belatacept + * Mycophenolate * Prednisone * Tacrolimus

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Belatacept, a CNI-free immunosuppressive option for kidney transplant patients, has shown improvements in renal function and a lower incidence of chronic allograft nephropathy compared to traditional treatments like cyclosporine.

Patients treated with belatacept also exhibited a more favorable metabolic profile and reduced formation of donor-specific antibodies, suggesting potential long-term benefits for kidney transplant outcomes, although further studies are needed to confirm these effects over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A safety evaluation of belatacept for the treatment of kidney transplant. Garcia, VD., Meinerz, G., Keitel, E.[2017]

A 61-year-old woman experienced acute vascular rejection of her kidney transplant 56 days after receiving belatacept, highlighting a potential risk associated with this immunosuppressive therapy.

The rejection was characterized by a predominance of cytotoxic memory T cells, suggesting that these cells may be resistant to the effects of belatacept, indicating a need for further investigation into the mechanisms of rejection in patients treated with this drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Acute Cellular Rejection With Detrimental Outcome Occurring Under Belatacept-Based Immunosuppressive Therapy: An Immunological Analysis. de Graav, GN., Hesselink, DA., Dieterich, M., et al.[2022]

Early conversion to belatacept-based immunosuppression after kidney transplantation significantly improved kidney function, as measured by eGFR, from 26.73 to 45.3 ml/min/1.73 m² within one year, while late conversion showed no significant change.

Both early and late conversion groups had a one-year allograft survival rate of 100%, but early conversion was associated with a higher rate of acute T-cell-mediated rejections, suggesting that the choice of immunosuppressants may influence rejection types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. Moein, M., Dvorai, RH., Li, BW., et al.[2023]

Belatacept, a new immunosuppressive drug for kidney transplantation, shows better cardiovascular and metabolic profiles compared to cyclosporin A, including lower blood pressure and serum lipids, and a reduced risk of new onset diabetes after transplantation.

While about 20% of patients on belatacept experienced adverse effects like anemia and infections, it does not appear to increase the risk of infections compared to cyclosporin A, making it a promising option for immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Introduction to the use of belatacept: a fusion protein for the prevention of posttransplant kidney rejection. Ippoliti, G., D'Armini, AM., Lucioni, M., et al.[2023]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

Belatacept is as effective as cyclosporine in preventing organ rejection in kidney transplant patients, with similar rates of patient and graft survival and acute rejection, while showing a significant advantage in reducing renal impairment after 12 months.

Patients treated with belatacept experienced fewer serious side effects, including lower rates of new-onset diabetes and better blood pressure and lipid levels compared to those on cyclosporine, indicating a potentially safer profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. Garnock-Jones, KP.[2016]

Belatacept shows improved renal function and lower rates of new onset diabetes compared to traditional calcineurin inhibitors (CNI) in kidney transplant recipients, based on a meta-analysis of six randomized controlled trials.

There were no significant differences in acute rejection rates between belatacept and CNIs, suggesting that belatacept may reduce CNI-related toxicity without compromising transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does belatacept improve outcomes for kidney transplant recipients? A systematic review. Talawila, N., Pengel, LH.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5724691/

Ten‐year outcomes in a randomized phase II study of kidney ... This post hoc analysis of a phase II study shows no difference at 10 years post–kidney transplant in cumulative rates for biopsy‐proven acute rejection.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1506027

Belatacept and Long-Term Outcomes in Kidney ... The reduction in the risk of death at 7 years was 38% with the more-intensive belatacept regimen and 45% with the less-intensive regimen as ...

3. nulojixhcp.bmscustomerconnect.com nulojixhcp.bmscustomerconnect.com/clinical-data/efficacy-failure.html

NULOJIX® (belatacept) | Clinical Data NULOJIX® (belatacept) regimen had a similar rate of efficacy failure vs CsA regimen1. *Patients may have experienced more than 1 event.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925001597

One-Year Outcomes After Belatacept Conversion in ... Overall, at 1-year follow-up, there were no significant differences in eGFR between patients on belatacept who remained free of rejection (52 [IQR: 43–67] ml/ ...

5. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.14412/full

Belatacept in Kidney Transplantation: Reflecting on the Past ... This regimen has proven to be highly effective, with biopsy-proven acute rejection (BPAR) rates of approximately 8%–12% within the first year ...

6. nulojixhcp.bmscustomerconnect.com nulojixhcp.bmscustomerconnect.com/pooled-safety.html

Selected Pooled Safety Data Summary of PTLD cases reported in NULOJIX kidney transplant trials through 36 months of treatment*. PTLD chart A mobile. *Empty boxes indicate 0. †In the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12341210/

Safety profile of belatacept in a real-life setting Belatacept is a co-stimulation blocker used in kidney transplant recipients to prevent allograft rejection. Unlike calcineurin inhibitors ...

8. bmsaccesssupport.com bmsaccesssupport.com/nulojix/indication-important-safety-information.html

NULOJIX® (belatacept) | Indication and Important Safety ... NULOJIX patients are at increased risk for PML, often a rapidly progressive and fatal opportunistic infection.

9. nulojixhcp.bmscustomerconnect.com nulojixhcp.bmscustomerconnect.com/clinical-data/renal-function.html

NULOJIX® (belatacept) | Clinical Data IMPORTANT SAFETY INFORMATION · Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss; consider reduction in ...

10. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/125288s075lbl.pdf

NULOJIX (belatacept) for injection, for intravenous use The data described below primarily derive from two randomized, active-controlled three-year trials of NULOJIX in de novo kidney transplant patients. In Study 1 ...