Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders

Multiple Myeloma Clinical Trial

— BMT  

Official title:

Combined Haploidentical Reduced Intensity Bone Marrow and Kidney Transplantation for Patients With Chronic Kidney Disease and Advanced Hematological Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01758042
• Other study ID #: 2012P001355
• Status: Recruiting
• Phase: N/A
• Start date: November 2012
• Est. completion date: July 2027

Study information

• Verified date: March 2023
• Source: Massachusetts General Hospital
• Contact: Yi-Bin A Chen, M.D.
• Phone: 617-724-1124
• Email: ychen6[@]partners.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: July 2027
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients ages 18-70

• Underlying hematological disorder which is potentially curable with allogeneic bone marrow transplantation. This includes, but is not limited to: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, multiple myeloma (MM), myelodysplastic syndrome (MDS), AL amyloidosis, diamond blackfan anemia, myelofibrosis or other myeloproliferative disease, sickle cell anemia, and thalassemia.

• Existence of haploidentical first degree relative who passes standard donor evaluations for bone marrow and kidney donation

• LVEF > 40% as measured by echocardiography or MUGA

• FEV1, FVC, and DLCO > 50% of predicted as measured by standard PFTs

• Total bilirubin < 2.0 (unless diagnosis of Gilbert's or hemolysis is made) and AST, ALT, alkaline phosphatase all < 5x institutions upper limit of normal

• ABO compatibility in the host vs. graft direction

• Men and women of reproductive potential must agree to use a reliable method of birth control during the treatment, and women should do so for a period of 1 year following the transplant.

• Participants should be on dialysis or have an estimated or measured CrCl < 35 ml/min

• Life expectancy greater than six months.

• Recipient ability to understand and provide informed consent

Exclusion Criteria:

• Active serious infection

• Participation in other investigational drug use at the time of enrollment

• Contraindication to therapy with any one of the proposed agents (e.g., history of allergy to rabbit serum in ATG)

• Serologic positivity for HIV, HCV, or HbsAg positivity

• ABO blood group incompatibility in the host-vs-graft direction

• Active serious infection

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• AL Amyloidosis
• Amyloidosis
• Anemia
• Anemia, Aplastic
• Anemia, Diamond-Blackfan
• Anemia, Sickle Cell
• Aplastic Anemia
• Autoimmune Diseases
• Chronic Kidney Disease
• Chronic Lymphocytic Leukemia (CLL)
• Chronic Myelogenous Leukemia (CML)
• Diamond Blackfan Anemia
• Hodgkin Disease
• Immunoglobulin Light-chain Amyloidosis
• Kidney Diseases
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Myelofibrosis
• Myeloproliferative Disease
• Myeloproliferative Disorders
• Non-Hodgkin's Lymphoma (NHL)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Renal Insufficiency, Chronic
• Sickle Cell Anemia
• Thalassemia

Intervention

Procedure:
• Haploidentical Bone Marrow/Kidney
Combined bone marrow and kidney transplantation using a haploidentical donor.

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients who are able to discontinue immunosuppressive therapy by one year post transplant		one year post transplant
Other	Number of patients who develop acute and chronic graft versus host disease (GVHD).		post transplant
Other	Number of patients who relapse from their underlying hematological disease		6 months, 1 year, and 2 years post transplant.
Primary	Number of patients who die of treatment-related complications.	Assess safety of haploidentical combined bone marrow and kidney transplantation as measured treatment related mortality.	100 days and 1 year post transplant
Secondary	Number of patients with acute and delayed renal allograft rejection		2 years post-transplant