Clinical trial NCT01758042: Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
Official title: Combined Haploidentical Reduced Intensity Bone Marrow and Kidney Transplantation for Patients With Chronic Kidney Disease and Advanced Hematological Disorders
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Kidney Disease
Acute Myeloid Leukemia (AML)
Acute Lymphoblastic Leukemia (ALL)
Chronic Myelogenous Leukemia (CML)
Chronic Lymphocytic Leukemia (CLL)
Non-Hodgkin's Lymphoma (NHL)
Hodgkin Disease
Multiple Myeloma
Myelodysplastic Syndrome (MDS)
Aplastic Anemia
AL Amyloidosis
Diamond Blackfan Anemia
Myelofibrosis
Myeloproliferative Disease
Sickle Cell Anemia
Autoimmune Diseases
Thalassemia
Keywords: Kidney
Chronic Kidney Disease
CKD
Bone Marrow
Bone Marrow Transplant
BMT
Leukemia
AML
ALL
CML
CLL
MM
NHL
MDS
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2012-12-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of patients who die of treatment-related complications.
timeFrame: 100 days and 1 year post transplant
Secondary outcomes:
measure: Number of patients with acute and delayed renal allograft rejection
timeFrame: 2 years post-transplant
Other outcomes:
measure: Number of patients who are able to discontinue immunosuppressive therapy by one year post transplant
timeFrame: one year post transplant
measure: Number of patients who develop acute and chronic graft versus host disease (GVHD).
timeFrame: post transplant
measure: Number of patients who relapse from their underlying hematological disease
timeFrame: 6 months, 1 year, and 2 years post transplant.
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Director of Clinical Research, Massachusetts General Hospital Bone Marrow Transplant Program
name: Yi-Bin A Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen YB, Elias N, Heher E, McCune JS, Collier K, Li S, Del Rio C, El-Jawahri A, Williams W, Tolkoff-Rubin N, Fishman JA, McAfee S, Dey BR, DeFilipp Z, O'Donnell PV, Cosimi AB, Sachs D, Kawai T, Spitzer TR. Haploidentical hematopoietic cell and kidney transplantation for hematological malignancies and end-stage renal failure. Blood. 2019 Jul 11;134(2):211-215. doi: 10.1182/blood.2019000775. Epub 2019 May 31.