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

(BMT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Yi-Bin A Chen, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Massachusetts General Hospital

Disqualifiers: Active infection, HIV, HCV, others

No Placebo Group

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to examine the outcome of a combined bone marrow and kidney transplant from a partially matched related (haploidentical or "haplo") donor. This is a pilot study, you are being asked to participate because you have a blood disorder and kidney disease. The aim of the combined transplant is to treat both your underlying blood disorder and kidney disease. We expect to have about 10 people participate in this study. Additionally, because the same person who is donating the kidney will also be donating the bone marrow, there may be a smaller chance of kidney rejection and less need for long-term use of anti-rejection drugs. Traditionally, very strong cancer treatment drugs (chemotherapy) and radiation are used to prepare a subject's body for bone marrow transplant. This is associated with a high risk for serious complications, even in subjects without kidney disease. This therapy can be toxic to the liver, lungs, mucous membranes, and intestines. Additionally, it is believed that standard therapy may be associated with a higher risk of a complication called graft versus host disease (GVHD) where the new donor cells attack the recipient's normal body. Recently, less intense chemotherapy and radiation regimens have been employed (these are called reduced intensity regimens) which cause less injury and GVHD to patients, and thus, have allowed older and less healthy patients to undergo bone marrow transplant. In this study, a reduced intensity regimen of chemotherapy and radiation will be used with the intent of producing fewer toxicities than standard therapy. Typical therapy following a standard kidney transplant includes multiple lifelong medications that aim to prevent the recipient's body from attacking or rejecting the donated kidney. These are called immunosuppressant drugs and they work by "quieting" the recipient's immune system to allow the donated kidney to function properly. One goal in our study is to decrease the duration you will need to be on immunosuppressant drugs following your kidney transplant as the bone marrow transplant will provide you with the donor's immune system which should not attack the donor kidney.

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 data supports the effectiveness of this treatment for blood disorders and chronic kidney disease?

Research shows that combining bone marrow and kidney transplants from partially matched donors can be effective. In a small study, most patients survived without disease relapse and maintained good kidney function. Another study found that this approach can help patients reduce or stop taking immune-suppressing drugs. ^{1 2 3 4 5}

Is the combined bone marrow and kidney transplant generally safe for humans?

The combined bone marrow and kidney transplant has been tested in humans, showing some risks like acute kidney injury and chronic kidney disease, but also long-term survival without disease relapse in some cases. Safety measures, such as adjusting drug doses and managing complications, have improved outcomes, with most patients avoiding severe complications like graft-versus-host disease. ^{1 2 6 7 8}

How is the Haploidentical Bone Marrow/Kidney Transplant treatment different from other treatments for blood disorders and chronic kidney disease?

This treatment is unique because it combines a bone marrow transplant with a kidney transplant from a half-matched (haploidentical) donor, aiming to treat both blood disorders and kidney failure simultaneously. It can potentially reduce the need for long-term immunosuppressive drugs by inducing tolerance to the donor organs, which is not typically achieved with standard treatments. ^{1 3 5 9 10}

Research Team

Yi-Bin A Chen, M.D.

Principal Investigator

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Haploidentical Bone Marrow/Kidney (Stem Cell Transplant)

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.

Participant Groups

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

Single Arm Study

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

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+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Haploidentical hematopoietic cell and kidney transplantation for hematological malignancies and end-stage renal failure. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Combined kidney and hematopoeitic cell transplantation to induce mixed chimerism and tolerance. [2022]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Long-term renal function after allogenic haematopoietic stem cell transplantation in adult patients: a single-centre study. [2010]

5. England pubmed.ncbi.nlm.nih.gov

Delayed kidney transplantation after HLA-haploidentical hematopoietic cell transplantation in a young woman with myelodysplastic syndrome with renal failure. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Acute kidney injury in paediatric bone marrow patients. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

Kidney transplantation for treatment of end-stage kidney disease after haematopoietic stem cell transplantation: case series and literature review. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

HLA-mismatched renal transplantation without maintenance immunosuppression. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Induction of kidney allograft tolerance after transient lymphohematopoietic chimerism in patients with multiple myeloma and end-stage renal disease. [2022]