Addition of Venetoclax to Combined Hematopoietic Stem Cell and Kidney Transplantation

Addition of Venetoclax to Combined Reduced Intensity Hematopoietic Stem Cell and Kidney Transplantation for Patients With Chronic Kidney Disease and Hematologic Malignancy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stem Cell Transplant; Tolerance; Stem Cell Transplant Complications; Hematologic Cancer; Kidney Failure Chronic
• Intervention / Treatment: Drug: Venetoclax; Procedure: Hematopoietic Cell Transplantation Conditioning Regimen; Procedure: Kidney Transplant; Procedure: Hematopoietic Cell Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Thomas Spitzer, MD; Phone Number: 617-724-1124; Email: tspitzer@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
      • Contact: Thomas Spitzer, MD; Phone Number: 617-724-1124; Email: tspitzer@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Recipient; Stem Cell and Kidney Transplant

Drug: Venetoclax; 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.; Procedure: Hematopoietic Cell Transplantation Conditioning Regimen; Cytoxan Day -6 & -5 Fludarabine Day -4, -3, -2 TBI Day -1; Procedure: Kidney Transplant; Living donor kidney transplant; Procedure: Hematopoietic 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of full donor chimerism		24 months
Incidence of Grade IV Toxicity due to Venetoclax	NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Days -8 to Days -1
Incidence of Grade V Toxicity due to Venetoclax	NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Days -8 to Days -1

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of acute renal allograft rejection	24 months
Incidence of delayed renal allograft rejection	24 months
Incidence of acute GVHD	24 months
Incidence of Chronic GVHD	24 months
Patient Survival Rate	24 months
Allograft Survival Rate	24 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: January 5, 2026
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Hematologic Diseases; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Renal Insufficiency, Chronic; Therapeutics; Surgical Procedures, Operative; Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Urologic Surgical Procedures; Urogenital Surgical Procedures; Renal Replacement Therapy; Organ Transplantation; venetoclax; Stem Cell Transplantation; Kidney Transplantation
• Other Study ID Numbers: DFCC 25-668

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No