Alemtuzumab Dosing for Bone Marrow Transplant

Overseen By Richard Cooper

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Disqualifiers: Anaphylaxis to alemtuzumab, Dialysis, Cancer, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 days

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adjusting the dose of alemtuzumab, a medication that weakens the immune system, can enhance the success of bone marrow transplants. The focus is on individuals undergoing these transplants for non-cancerous conditions. Participants must receive alemtuzumab as part of their treatment plan and have a fully matched stem cell donor. The study aims to determine the optimal dose to use on the day of the transplant to help the body accept the new cells. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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 trial coordinators or your doctor.

Is there any evidence suggesting that alemtuzumab is likely to be safe for humans?

Research has shown that alemtuzumab is generally safe, though some risks exist. Studies have found that it can reduce the likelihood of complications such as GvHD (where donor cells attack the recipient's body) and TRM (transplant-related mortality) following a bone marrow transplant. However, it carries a higher risk of infections and thyroid issues.

Previous treatment data suggest that alemtuzumab is usually well-tolerated under medical supervision. Alemtuzumab's approval for other uses indicates a certain level of safety. Nonetheless, monitoring for side effects remains important with any medical treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about alemtuzumab for bone marrow transplants because it offers a targeted approach to reducing immune rejection. Unlike standard conditioning regimens that can involve high doses of chemotherapy or radiation, alemtuzumab specifically targets and depletes T-cells. This selective action aims to minimize the risk of graft-versus-host disease while potentially improving transplant success rates. Furthermore, its subcutaneous administration is less invasive compared to traditional intravenous methods, potentially enhancing patient comfort and compliance.

What evidence suggests that alemtuzumab might be an effective treatment for bone marrow transplant?

Research has shown that alemtuzumab, which participants in this trial will receive, can help prepare patients for bone marrow transplants. One study found that patients who received alemtuzumab experienced significantly less graft-versus-host disease (GVHD), a common issue after a transplant. Another study demonstrated that alemtuzumab helps prevent graft failure, increasing the likelihood that the body will accept the transplanted cells. These findings suggest that alemtuzumab can enhance transplant success by reducing complications. Overall, promising evidence indicates that it can make transplants safer and more effective. ^{6 7 8 9 10}

Who Is on the Research Team?

Parinda Mehta, MD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Are You a Good Fit for This Trial?

This trial is for patients aged 6 weeks to 30 years who need a bone marrow transplant due to non-malignant diseases and are getting an alemtuzumab-based treatment. Initially, only those with a perfect donor match or receiving selected stem cells can join. After review, others may be eligible. Exclusions include life expectancy under 4 weeks, previous alemtuzumab use without clearance, dialysis or plasmapheresis at the start of treatment, cancer diagnosis, severe skin conditions preventing subcutaneous dosing, and history of allergy to alemtuzumab.

Inclusion Criteria

I am between 6 weeks and 30 years old.

I have a perfect match donor for my stem cell transplant.

I am getting a stem cell transplant with alemtuzumab for a non-cancerous disease.

Exclusion Criteria

I have not signed and cannot sign the informed consent form.

Life expectancy less than 4 weeks

I cannot receive injections due to severe skin conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive alemtuzumab subcutaneously over days -14, -13, and -12 in preparation for allogeneic hematopoietic cell transplant

3 days

3 visits (in-person)

Transplantation

Day 0 is the planned day of graft infusion for allogeneic hematopoietic cell transplant

1 day

1 visit (in-person)

Follow-up

Participants are monitored for alemtuzumab levels, acute GVHD, mixed chimerism, and immune recovery

100 days

What Are the Treatments Tested in This Trial?

Interventions

• Alemtuzumab

Trial Overview The study tests if adjusting the dose of Alemtuzumab can achieve optimal levels in the blood on Day 0 (day of graft infusion) for better outcomes in allogeneic hematopoietic cell transplantation (HCT). The goal is to maintain drug levels between 0.2-0.6 ug/mL.

How Is the Trial Designed?

Group I: Alemtuzumab Experimental Treatment 1 Intervention

Patients will be given 10 mg/m2 alemtuzumab divided over days -14, -13, and -12. The first dose should be limited to no more than 3 mg per the manufacturer's recommendation. If the calculated daily dose is greater than 3 mg, the first dose (day -14) should be limited to 3 mg and the remainder of the dosing should be divided over days -13 and -12. Alemtuzumab will be drawn into a sterile syringe and given to patients subcutaneously.

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

Approved in United States as Campath for:

• Chronic lymphocytic leukemia
• Multiple sclerosis

Approved in European Union as Lemtrada for:

• Multiple sclerosis

Approved in European Union as Campath for:

• Chronic lymphocytic leukemia

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

Published Research Related to This Trial

In a study of 11 kidney transplant recipients, alemtuzumab induction led to a high patient and graft survival rate of 91% at one year, indicating its efficacy as an induction agent in renal transplantation.

The use of alemtuzumab was found to be safe, with no serious adverse events such as hyperlipidemia or new-onset diabetes, and no cases of acute rejection were observed, even among recipients of extended criteria donor kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab induction in deceased donor kidney transplantation. Shin, M., Song, SH., Kim, JM., et al.[2017]

A population pharmacokinetic model for alemtuzumab was developed using data from 206 pediatric patients, revealing that body weight significantly affects the drug's clearance and distribution, which can lead to variable drug exposure.

The study suggests that the current standard dosing method may not be optimal for all children, and individualized dosing based on this model could improve treatment outcomes and reduce toxicity associated with alemtuzumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome. Admiraal, R., Jol-van der Zijde, CM., Furtado Silva, JM., et al.[2023]

In a study of 37 high-risk leukemia patients undergoing transplantation, a low dose of 10-20 mg of alemtuzumab was used, resulting in rapid neutrophil and platelet engraftment with minimal severe acute graft-versus-host disease (GvHD) cases.

After a median follow-up of 371 days, 70% of patients were alive and in complete remission, indicating that this dosing strategy is effective and safe for patients undergoing allogeneic transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and clinical activity of very low-dose alemtuzumab in transplantation for acute leukemia. Spyridonidis, A., Liga, M., Triantafyllou, E., et al.[2021]

In a study of 53 children undergoing hematopoietic stem cell transplantation, high exposure to alemtuzumab was linked to delayed T-cell reconstitution and an increased risk of graft failure, highlighting the need for careful dosing.

The developed pharmacokinetics model allows for individualized dosing of alemtuzumab, aiming to optimize T-cell recovery and minimize graft failure in pediatric patients with nonmalignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-response analysis of alemtuzumab in pediatric allogeneic HSCT for nonmalignant diseases: the ARTIC study. Achini-Gutzwiller, FR., Schilham, MW., von Asmuth, EGJ., et al.[2023]

In a study of 10 kidney transplant recipients treated with alemtuzumab, long-term immunosuppressive therapy was found to influence the balance of T-regulatory and Th17 cells, which are important for immune response regulation.

The research demonstrated that T-regulatory cells can effectively suppress Th17 cell activity, suggesting a potential mechanism for managing immune responses in patients undergoing long-term immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Th17 cells in alemtuzumab-treated patients: the effect of long-term maintenance immunosuppressive therapy. Hester, J., Mills, N., Shankar, S., et al.[2022]

Alemtuzumab (Campath 1H), a monoclonal antibody targeting CD52 on B and T cells, is increasingly used as a conditioning agent for bone marrow transplantation, but it can have serious side effects.

In a case study of a 37-year-old woman, acute renal failure and disseminated intravascular coagulation (DIC) occurred after receiving Campath, leading to the abortion of her transplant and ongoing dialysis, highlighting the need for caution and further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute renal failure and disseminated intravascular coagulation following an idiosyncratic reaction to Alemtuzumab (Campath 1H) or fludarabine. Osborne, WL., Lennard, AL.[2017]

A study involving 29 pediatric and young adult patients showed that individualized dosing of alemtuzumab, based on body weight or surface area, can optimize drug levels for better outcomes in hematopoietic cell transplantation (HCT).

The research identified a specific therapeutic range for alemtuzumab (0.15-0.6 μg/mL) that is associated with improved HCT results, highlighting the importance of precise dosing to achieve effective lymphodepletion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-informed precision dosing for alemtuzumab in paediatric and young adult patients undergoing allogeneic haematopoietic cell transplantation. Dong, M., Emoto, C., Fukuda, T., et al.[2022]

In a study of 12 patients with aggressive CD52-positive hematologic malignancies, low-dose alemtuzumab (10 mg daily) combined with cyclophosphamide and total body irradiation effectively prevented grade III/IV acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, with no cases reported.

All patients experienced rapid engraftment, achieving significant donor chimerism by 3 months post-transplant, and at a median follow-up of 14.7 months, seven patients were alive and five were disease-free.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose alemtuzumab (Campath) in myeloablative allogeneic stem cell transplantation for CD52-positive malignancies: decreased incidence of acute graft-versus-host-disease with unique pharmacokinetics. Khouri, IF., Albitar, M., Saliba, RM., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6849949/

Similar outcomes of alemtuzumab-based hematopoietic ... A retrospective comparison from the European Blood and Marrow Transplant Registry reported a significant reduction in acute and chronic GVHD ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6885503/

Population Pharmacokinetics of Alemtuzumab (Campath) in ... Alemtuzumab (Campath®) is used to prevent graft-versus-host disease and graft failure following pediatric allogeneic hematopoietic cell ...

3. astctjournal.org astctjournal.org/article/S1083-8791(13)00498-9/pdf

Long-Term Outcomes of Alemtuzumab-Based Reduced- ... A recent large Center for International Blood and Marrow. Transplant Research (CIBMTR) analysis reported 5-yr OS of. 33% for RIC protocols (mainly T cell ...

4. nature.com nature.com/articles/s41409-023-02144-8

Alemtuzumab treatment for steroid-refractory acute graft ... Alemtuzumab treatment for steroid-refractory acute graft-versus-host disease leads to severe immunosuppression but not to relapse of malignant disease.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2473952920318279

Similar outcomes of alemtuzumab-based hematopoietic ... A retrospective comparison from the European Blood and Marrow Transplant Registry reported a significant reduction in acute and chronic GVHD ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8032381/

Safety of Alemtuzumab and Autologous Hematopoietic ... We confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2001/alemmil050701LB.htm

Campath (ALEMTUZUMAB) Package Insert WARNING. Campath should be administered under the supervision of a physician experienced in the use of antineoplastic therapy.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3126913/

Alemtuzumab in allogeneic hematopoetic stem cell ... Alemtuzumab is a safe and effective drug that can reduce both GvHD and TRM after transplant. The side-effects are an increased risk of disease recurrence.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT00328198

Subcutaneous Alemtuzumab (CAMPATH®, MabCampath® ... An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule ...

10. astctjournal.org astctjournal.org/article/S1083-8791(07)00510-1/fulltext

Alemtuzumab for the Treatment of Steroid-Refractory Acute ... The purpose of this study was to evaluate the safety and efficacy of alemtuzumab in treating steroid-refractory aGVHD (≥grade II) following HSCT.