Hand Transplant + Belatacept for Limb Loss Therapy

Overseen By Linda Cendales, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Linda Cendales

Disqualifiers: Active malignancy, Immunodeficiency, 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

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a hand transplant, combined with the immunosuppressant Belatacept, can help individuals who have lost a limb below the elbow regain daily function. Researchers will assess how well the new hand performs in everyday tasks 18 months post-transplant. The trial suits those who have lost a limb and can travel for regular check-ups and tests. Participants should be aware of potential risks, such as rejection or infection of the transplanted hand. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team to understand any specific requirements.

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

Research shows that hand transplants can sometimes lead to serious problems, such as the body rejecting the new hand or developing an infection. For example, one study found that a transplanted hand had to be removed after several years due to these issues. Another report described a patient who switched to Belatacept after experiencing rejection with a different medication. This switch occurred because Belatacept might better manage these problems.

Overall, researchers continue to study hand transplants using Belatacept closely. The goal is to find the best ways to reduce risks and improve outcomes. While risks exist, this research aims to determine how safe and effective these treatments can be for individuals who have lost a hand or arm. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using belatacept with hand transplants for limb loss because belatacept offers a novel way to prevent the body from rejecting the new limb. Unlike traditional immunosuppressants that can have a broad range of side effects, belatacept specifically targets a pathway critical for immune activation, potentially reducing complications. This targeted approach not only aims to improve the success rate of transplants but also enhances the patient's quality of life by minimizing the need for more aggressive immune suppression.

What evidence suggests that hand transplantation with Belatacept could be an effective treatment for limb loss?

Research has shown that hand transplants can restore movement and feeling in a new hand. Studies have found that patients often regain the ability to perform everyday tasks, an important sign of success. In this trial, participants will receive a hand transplant with Belatacept, a drug that helps prevent rejection of the new hand and may improve outcomes. Previous patients have experienced better movement and feeling with these transplants. Although risks like rejection and infection exist, the procedure can significantly enhance the quality of life for those who have lost a limb. ^{4 6 7 8 9}

Who Is on the Research Team?

Linda Cendales, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-65 who have lost a limb below the elbow and are willing to give informed consent. Participants must be able to travel to the study site or send samples by mail. People with conditions that affect follow-up, increase risk, or confound data interpretation, active malignancies, unwillingness to comply with monitoring and therapy, or immunodeficiency syndromes cannot join.

Inclusion Criteria

I am willing and legally able to agree to participate.

Willingness to travel to study site for protocol specific samples to be taken, or in some cases, the ability to send samples via overnight mail

Exclusion Criteria

Any condition that would likely increase the risk of protocol participation or confound the interpretation of the data

I have or had cancer or lymphoma.

Any condition that precludes serial follow-up

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo hand transplantation and initial recovery

4-6 weeks

Multiple visits for surgery and immediate post-operative care

Treatment and Monitoring

Participants receive immunosuppressive medications and are monitored for rejection and infection

18 months

Regular visits for medical evaluations, blood tests, biopsies, and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept
• Hand transplant

Trial Overview The study tests the safety and effectiveness of hand transplants using Belatacept for immunosuppression in patients with limb loss. The main goal is assessing if patients can use their new hand for daily activities after 18 months. It involves visits over this period for various evaluations including blood tests and biopsies.

How Is the Trial Designed?

Group I: Hand transplant with Belatacept Experimental Treatment 2 Interventions

Belatacept is already approved in United States, European Union for the following indications:

Approved in United States as Nulojix for:

• Prophylaxis of organ rejection in adult patients receiving a kidney transplant

Approved in European Union as Nulojix for:

• Prophylaxis of organ rejection in adult patients receiving a kidney transplant

Who Is Running the Clinical Trial?

Linda Cendales

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

Belatacept is an effective immunosuppressant for kidney transplant recipients, showing noninferior patient and allograft survival compared to cyclosporine in Phase 3 trials, with improved kidney function over three years.

While belatacept may offer benefits like better renal function and cardiometabolic health, it carries a risk of higher early rejection rates and potential increased risk of posttransplant lymphoproliferative disease, particularly in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. Wojciechowski, D., Vincenti, F.[2018]

In a case study of a hand transplant recipient, switching from traditional calcineurin inhibitors to belatacept and sirolimus successfully resolved acute rejection and nephrotoxicity, suggesting belatacept may be a safer alternative for immunosuppression in vascularized composite allotransplantation (VCA).

Belatacept could provide effective rejection prophylaxis with fewer side effects compared to conventional therapies, which is particularly important for patients undergoing VCA for non-life-threatening conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tacrolimus to Belatacept Conversion Following Hand Transplantation: A Case Report. Cendales, L., Bray, R., Gebel, H., et al.[2023]

Belatacept, an emerging treatment for kidney transplantation, was well tolerated in four hand-transplanted patients and may help reduce the need for nephrotoxic calcineurin inhibitors, potentially preserving kidney function.

While belatacept showed promise in improving immunosuppression strategies, one patient experienced severe rejection and complications, highlighting the need for careful monitoring of the immunologic state during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and limitations of belatacept in 4 hand-transplanted patients. Grahammer, J., Weissenbacher, A., Zelger, BG., et al.[2023]

Belatacept, a CD28/B7 inhibitor, has been successfully used as a primary immunosuppressant in a hand transplant recipient, allowing for a transition to a CNI-free regimen.

This case highlights that belatacept can effectively prevent organ rejection while avoiding the chronic side effects associated with traditional calcineurin inhibitors, which is particularly beneficial for nonlifesaving transplants like vascularized composite allotransplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De novo belatacept in clinical vascularized composite allotransplantation. Cendales, LC., Ruch, DS., Cardones, AR., et al.[2023]

An accurate and precise assay for measuring belatacept serum concentrations was developed, showing a measurement range of 0.9-30 mg/L and high accuracy (91%-99%).

This assay was applied in a pharmacokinetic study involving 5 renal transplant recipients, allowing for the visualization of belatacept concentrations over time, which is crucial for optimizing immunosuppressive therapy post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Klaasen, RA., Egeland, EJ., Chan, J., et al.[2019]

Belatacept, a new immunosuppressant for kidney transplantation, has shown superior graft function and better preservation of renal structure compared to traditional treatments like cyclosporine, based on phase II and III clinical trials.

However, belatacept is associated with a higher risk of cellular rejection and post-transplant lymphoproliferative disorder (PTLD), particularly in patients who are EBV seronegative, indicating the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: from rational design to clinical application. Wekerle, T., Grinyó, JM.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25401735/

Hand and upper extremity transplantation: an update of ... Results: Although 24 losses (including four mortalities) are known, three of the four reported mortalities and eight of 24 limb losses were caused by multiple ...

2. link.springer.com link.springer.com/article/10.1007/s10856-017-5880-0

Outcomes after hand and upper extremity transplantation This review will discuss the current state of HUET, summarizing outcome data on graft survival, motor and sensory function, as well as immunosuppressive ...

3. researchgate.net researchgate.net/publication/396021583_The_Current_Status_of_Vascularized_Composite_Allotransplantation

The Current Status of Vascularized Composite ... ... hand and upper limb transplants have been performed by the UK Hand Transplant Programme. We report functional outcomes for our first six ...

4. journals.sagepub.com journals.sagepub.com/doi/10.1177/1558944718790579

Building a Hand and Upper Extremity Transplantation ... The emerging field of vascularized composite allotransplantation (VCA) offers promising functional and aesthetic outcomes when compared with conventional ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10235447/

Challenges and opportunities in vascularized composite ... Vascularized composite allotransplantation (VCA) is a relatively new field that offers functional restoration of severely damaged limbs. Joint ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02165865

Vascularized Composite Allotransplantation of the Hand ... Hand transplantation includes transferring upper extremities/hands from deceased human donors to patients with single or bilateral hand or arm amputation. The ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7756600/

Long‐term outcome after hand and forearm transplantation One hand allograft eventually developed severe allograft vasculopathy and was amputated at 7 years. The patient later died due to progressive gastric cancer.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522003458

Case Report Tacrolimus to Belatacept Conversion ... Herein, we report on the case of a hand transplant recipient who developed recurrent acute rejection with alloantibody formation and concomitant calcineurin ...

9. researchgate.net researchgate.net/publication/288663550_Functional_Outcomes_after_Bilateral_Hand_Transplantation_A_35-Year_Comprehensive_Follow-Up

Functional Outcomes after Bilateral Hand Transplantation ... Since the first successful hand transplant in 1998 (1), over 115 patients have undergone facial (43%) and upper extremity VCA (57%) (2).