Kidney Failure Chronic, Stem Cell Transplant, Stem Cell Transplant Complications, Tolerance, Hematologic Cancer
Conditions
Brief summary
The primary objective is to assess the safety of the addition of venetoclax to reduced intensity conditioning for HLA-matched and haploidentical combined HSC and kidney transplantation as measured by stable full donor hematopoiesis and absence of CTCAE grade IV or V toxicity attributable to venetoclax.
Interventions
DRUGVenetoclax
Venetoclax 400mg orally once daily on days -8 through -1 with daily monitoring for tumor lysis syndrome. Venetoclax tablets will be swallowed (not crushed). Venetoclax dosing will not be repeated in the event of vomiting.
Cytoxan Day -6 \& -5 Fludarabine Day -4, -3, -2 TBI Day -1
PROCEDUREKidney Transplant
Living donor kidney transplant
PROCEDUREHematopoietic Cell Transplantation
Donor bone marrow (target of 4 x 108 nucleated cells/kg of recipient ideal body weight) PBSC A goal dose of 5 x 106 CD34+ cells / kg of recipient actual body weight will be infused (minimum acceptable is 2 x 106 CD34+ cells / kg).
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Patient ages 18-70 * Underlying hematological malignancy which is deemed as being potentially curable with allogeneic bone marrow or PBSC transplantation by the BMT voting team. * Hematological malignancies include, but are 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. Patient should be in a partial (PR) or complete remission (CR) at the time of the transplant. * Existence of an HLA-matched or haploidentical 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 a CrCl ≤ 35 ml/min * Life expectancy greater than 6 months * Recipient ability to understand and provide informed consent Donor Inclusion Criteria: * HLA matched or haploidentical relative as defined by 3/6, 4/6, or 5/6 HLA-matched at HLA -A, -B, or -DRB1 who is 18-70 years of age * ECOG performance status 0 or 1 * Excellent health per conventional pre-donor history (medical and psychosocial evaluation) • Acceptable laboratory parameters (hematology in normal or near-normal range; liver function \< 3 times the upper limit of normal and normal creatinine) * Compatible ABO blood group * Negative donor lymphocyte cross match * No positive testing for active viral infection (Hepatitis B, Hepatitis C, HIV) * Donor ability to understand and provide informed consent * Meets standard institutional criteria for both bone marrow or peripheral blood stem cell (PBSC) and kidney donation
Exclusion criteria
* Active serious infection * Participation in other investigational drug use at the time of enrollment * Positivity for active infection with HIV, HCV, or HBV * ABO blood group incompatibility in the host-vs-graft direction
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of full donor chimerism | 24 months | — |
| Incidence of Grade IV Toxicity due to Venetoclax | Days -8 to Days -1 | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| Incidence of Grade V Toxicity due to Venetoclax | Days -8 to Days -1 | NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
Secondary
| Measure | Time frame |
|---|---|
| Incidence of acute renal allograft rejection | 24 months |
| Incidence of delayed renal allograft rejection | 24 months |
| Incidence of Chronic GVHD | 24 months |
| Incidence of acute GVHD | 24 months |
| Patient Survival Rate | 24 months |
| Allograft Survival Rate | 24 months |
Countries
United States
Contacts
CONTACTThomas Spitzer, MD
Outcome results
None listed