Addition of Venetoclax to Combined Hematopoietic Stem Cell and Kidney Transplantation

NCT07358195 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: DFCC 25-668
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Failure Chronic; Stem Cell Transplant; Stem Cell Transplant Complications; Tolerance; Hematologic Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• 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

Study Arms (1)

Recipient

EXPERIMENTAL

Stem Cell and Kidney Transplant

Drug: Venetoclax; Procedure: Hematopoietic Cell Transplantation Conditioning Regimen; Procedure: Kidney Transplant; Procedure: Hematopoietic Cell Transplantation

Interventions

Venetoclax DRUG

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.

Recipient

Hematopoietic Cell Transplantation Conditioning Regimen PROCEDURE

Cytoxan Day -6 \& -5 Fludarabine Day -4, -3, -2 TBI Day -1

Recipient

Kidney Transplant PROCEDURE

Living donor kidney transplant

Recipient

Hematopoietic Cell Transplantation PROCEDURE

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).

Recipient

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Hematologic Neoplasms

Interventions

venetoclax; Kidney Transplantation; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Organ Transplantation; Transplantation; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy

Central Study Contacts

Thomas Spitzer, MD

CONTACT

617-724-1124; tspitzer@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Harvard Medical School Director Emeritus, Bone Marrow Transplant Program

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 22, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 22, 2026

Record last verified: 2025-12

Locations

US (1)