Bone Marrow/Kidney Transplant for Blood Disorders & Chronic Kidney Disease

(BMT Trial)

Overseen By Yi-Bin Chen, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: Active infection, HIV, HCV, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to explore the effectiveness of a combined bone marrow and kidney transplant from a partially matched (haploidentical) donor. Known as Haploidentical Bone Marrow/Kidney Transplant, this approach seeks to treat blood disorders, such as leukemia or sickle cell anemia, and chronic kidney disease while reducing the risk of kidney rejection and the need for long-term anti-rejection drugs. The trial employs a milder form of chemotherapy and radiation, potentially resulting in fewer side effects compared to traditional methods. This trial may suit individuals with certain blood disorders and kidney disease who have a related donor willing to provide both bone marrow and a kidney. As an unphased trial, it offers a unique opportunity to explore innovative treatment options that could potentially improve quality of life.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since this involves a bone marrow and kidney transplant, it's possible that some medications might need to be adjusted. Please discuss this with the trial team for specific guidance.

What prior data suggests that this combined bone marrow and kidney transplant is safe?

Research has shown that combining bone marrow and kidney transplants from a partially matched family member, known as haploidentical transplants, is generally safe and feasible. Studies have found that using cyclophosphamide after the transplant helps control the immune response, reducing the risk of complications.

A gentler form of chemotherapy and radiation, called reduced intensity regimens, is also employed. This approach aims to minimize damage to organs like the liver and lungs and lower the risk of graft versus host disease (GVHD), where new donor cells attack the recipient's body. This method is designed to enhance safety, even for individuals with existing health issues.

Overall, these strategies aim to reduce the need for long-term use of immunosuppressive drugs, making the process less demanding on the body compared to traditional methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Haploidentical Bone Marrow/Kidney treatment is unique because it combines both a bone marrow and a kidney transplant from a partially matched donor, which is not typical for treating blood disorders and chronic kidney disease. This dual approach has the potential to address the underlying blood disorder while simultaneously restoring kidney function, offering a comprehensive solution that current treatments, like dialysis or standard bone marrow transplants, cannot achieve alone. Researchers are excited about this treatment because it could significantly improve patient outcomes by tackling both issues with one procedure, potentially reducing the need for long-term kidney dialysis and frequent medical interventions.

What evidence suggests that this combined bone marrow and kidney transplant could be effective for blood disorders and kidney disease?

Research has shown that combining a bone marrow and kidney transplant from a partially matched family member can help treat blood disorders and kidney disease. In this trial, participants will receive a Haploidentical Bone Marrow/Kidney transplant, which earlier studies have shown to provide good control over these diseases. The bone marrow transplant transfers the donor’s immune system to the recipient, potentially lowering the risk of kidney rejection. This approach could also reduce the need for long-term use of anti-rejection drugs. Using less intense chemotherapy and radiation in this method aims to avoid many severe side effects associated with traditional treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Yi-Bin A Chen, M.D.

Principal Investigator

Director of Clinical Research, Massachusetts General Hospital Bone Marrow Transplant Program

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with certain blood disorders (like leukemia, lymphoma, myeloma) and chronic kidney disease who have a related donor that partially matches their bone marrow and can donate a kidney. Participants must have reasonable lung and heart function, agree to birth control measures, not be HIV or hepatitis positive, and cannot be part of another drug study.

Inclusion Criteria

You are expected to live for more than six months.

Your lung function tests show that you can breathe out, breathe in, and transfer oxygen normally.

Your heart's pumping function is good, as measured by a heart ultrasound or a special heart scan.

Exclusion Criteria

Participation in other investigational drug use at the time of enrollment

I have tested positive for HIV, Hepatitis C, or Hepatitis B.

I am currently fighting a serious infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation

Participants undergo reduced intensity chemotherapy and radiation to prepare for the bone marrow transplant

2-3 weeks

Transplantation

Participants receive a combined bone marrow and kidney transplant from a haploidentical donor

1 week

Initial Follow-up

Participants are monitored for safety and effectiveness, focusing on treatment-related complications

100 days

Long-term Follow-up

Participants are monitored for long-term outcomes, including graft survival and reduction in immunosuppressant use

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Haploidentical Bone Marrow/Kidney

Trial Overview

The study tests a combined bone marrow and kidney transplant from the same family donor to treat both blood disorders and kidney disease. It uses less intense chemotherapy before the transplant in hopes of reducing complications like organ damage or graft versus host disease.

How Is the Trial Designed?

Group I: Haploidentical Bone Marrow/Kidney Experimental Treatment 1 Intervention

Single Arm Study

Haploidentical Bone Marrow/Kidney is already approved in United States, European Union, Japan, China for the following indications:

Approved in United States as Haploidentical Bone Marrow Transplant for:

• Blood disorders
• Kidney disease
• Leukemia
• Lymphoma
• Sickle cell disease

Approved in European Union as Haploidentical Hematopoietic Cell Transplantation for:

• Hematologic malignancies
• Sickle cell disease
• Kidney disease

Approved in Japan as Haploidentical Bone Marrow Transplant for:

• Leukemia
• Lymphoma
• Myeloid malignancies

Approved in China as Haploidentical Hematopoietic Cell Transplantation for:

• Leukemia
• Lymphoma
• Myeloid malignancies

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Published Research Related to This Trial

Bone marrow transplantation (BMT) has significantly improved outcomes for various diseases, but it carries a risk of renal complications, with 5% to 15% of patients developing acute kidney injury (AKI) and 5% to 20% experiencing chronic renal failure (CRF).

Identifying and managing risk factors for AKI, such as drug toxicity and preexisting kidney issues, is essential, as AKI can lead to long-term kidney dysfunction; however, advancements in BMT techniques and risk management have led to a decline in the rates of both AKI and CRF over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute kidney injury in paediatric bone marrow patients. Detaille, T., Anslot, C., de Cléty, SC.[2019]

In a study of six patients who received kidney transplants (KT) after hematopoietic stem cell transplants (HSCT) for various blood diseases, all patients survived and maintained good kidney function over a median follow-up of 51 months.

Although there was a high incidence of infections, only one patient experienced acute rejection, and none had a recurrence of their original blood disease, suggesting that the management strategies used were effective in ensuring positive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kidney transplantation for treatment of end-stage kidney disease after haematopoietic stem cell transplantation: case series and literature review. Tsuchimoto, A., Masutani, K., Omoto, K., et al.[2021]

Hematopoietic stem cell transplant (HSCT) patients face a high risk of acute kidney injury (AKI) and chronic kidney disease (CKD), which can lead to increased morbidity and mortality, highlighting the need for careful monitoring of kidney function in these patients.

While the exact cause of CKD in HSCT patients is often unknown, conditions like graft vs host disease and thrombotic microangiopathy are significant contributors, and kidney transplantation is considered a safe option for those who develop end-stage renal disease (ESRD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The kidney effects of hematopoietic stem cell transplantation. Sawinski, D.[2022]

A pilot trial at Massachusetts General Hospital involving 6 patients demonstrated that simultaneous hematopoietic cell and kidney transplantation from HLA-haploidentical donors is feasible, with 4 out of 6 patients remaining alive and free from disease relapse after the procedure.

The study showed promising safety outcomes, with no significant cases of acute graft-versus-host disease (GVHD) and only one case of moderate chronic GVHD, suggesting that the combination of post-transplant medications effectively managed GVHD risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic cell and kidney transplantation for hematological malignancies and end-stage renal failure. Chen, YB., Elias, N., Heher, E., et al.[2021]

A 31-year-old woman with myelodysplastic syndrome and end-stage renal disease successfully underwent a haploidentical allogeneic hematopoietic cell transplantation (alloHCT) while on hemodialysis, demonstrating the feasibility of this approach for patients typically excluded from such procedures.

Fourteen months post-alloHCT, she received a kidney transplant from the same donor, which eliminated the need for additional immunosuppression, highlighting a potential strategy for managing patients with concurrent hematologic malignancies and renal failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed kidney transplantation after HLA-haploidentical hematopoietic cell transplantation in a young woman with myelodysplastic syndrome with renal failure. Miller, KC., Hall, AC., Cohen-Bucay, A., et al.[2022]

The study involved two female patients with end-stage renal disease due to multiple myeloma who successfully received combined kidney and bone marrow transplants, achieving donor-specific tolerance and sustained anti-tumor effects without the need for long-term immunosuppression.

Both patients showed rapid normalization of kidney function and significant declines in urinary kappa light chains, indicating effective treatment of their myeloma, with no rejection episodes reported for nearly 4 years and 2 years, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. Bühler, LH., Spitzer, TR., Sykes, M., et al.[2022]

In a study at Stanford University Medical Center, combined kidney and hematopoietic cell transplantation successfully induced mixed chimerism and immune tolerance in most fully HLA matched patients, allowing for complete withdrawal of immunosuppressive drugs.

Haplotype matched patients also showed promising results, achieving persistent mixed chimerism and partial withdrawal of immunosuppressive therapy, indicating potential for broader applications in transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined kidney and hematopoeitic cell transplantation to induce mixed chimerism and tolerance. Lowsky, R., Strober, S.[2022]

In a study involving five patients with end-stage renal disease, combined bone marrow and kidney transplants led to successful outcomes for four patients, allowing them to stop immunosuppressive therapy 9 to 14 months post-transplant, with stable renal function maintained for 2 to 5.3 years.

The presence of donor-specific unresponsiveness in T cells and high levels of FOXP3 mRNA in biopsies after stopping immunosuppressive therapy suggests a potential mechanism for tolerance to the transplanted kidney, although one patient experienced irreversible humoral rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-mismatched renal transplantation without maintenance immunosuppression. Kawai, T., Cosimi, AB., Spitzer, TR., et al.[2022]

In a study involving five patients with end-stage renal disease who underwent a modified combined kidney and bone marrow transplantation (CKBMT), transient multilineage mixed chimerism was observed, indicating a temporary state where the recipient's immune system coexists with donor cells.

One patient showed early signs of donor-specific unresponsiveness, suggesting that the modified CKBMT protocol may promote tolerance to the donor organ, which is crucial for long-term transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mixed chimerism, lymphocyte recovery, and evidence for early donor-specific unresponsiveness in patients receiving combined kidney and bone marrow transplantation to induce tolerance. LoCascio, SA., Morokata, T., Chittenden, M., et al.[2021]

In a study of 123 allogeneic HSCT patients, 40% developed chronic kidney disease (CKD) within 24 months, with age over 45, early acute kidney injury, and a baseline GFR below 90 ml/min/1.73 m² identified as significant risk factors.

Among patients with CKD at 24 months, 67% continued to have CKD after 36 months, highlighting the need for ongoing renal function monitoring, particularly in older patients with existing kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term renal function after allogenic haematopoietic stem cell transplantation in adult patients: a single-centre study. Touzot, M., Elie, C., van Massenhove, J., et al.[2010]

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