Venetoclax for Transplant Complications

Overseen By Thomas Spitzer, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Massachusetts General Hospital

Disqualifiers: Active infection, HIV, HCV, HBV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of adding venetoclax, a medication, to the standard treatment for individuals undergoing combined stem cell and kidney transplants. The focus is on those with blood-related cancers, such as leukemia or lymphoma, who are in partial or complete remission and have a donor match. The trial aims to ensure the treatment does not cause severe side effects while supporting successful transplants. Suitable candidates have a blood-related cancer in remission, are on dialysis or have reduced kidney function, and have a matched donor relative. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the chance to contribute to groundbreaking medical advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that venetoclax is likely to be safe for humans?

Research has shown that venetoclax is generally safe and well-tolerated by patients. One study combined venetoclax with other treatments for patients who had undergone a stem cell transplant. The results indicated safety for these patients, with most side effects being manageable. Another study found that venetoclax provided benefits without causing serious issues, even for those at high risk of disease recurrence. While six patients died, five deaths resulted from disease recurrence and one from transplant-related complications, not directly from venetoclax. This suggests that venetoclax is a relatively safe option when used after transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Venetoclax in the context of transplant complications because, unlike standard treatments that primarily focus on immunosuppression, Venetoclax targets and inhibits the BCL-2 protein. This protein plays a role in cell survival, and its inhibition can help eliminate problematic cells that might cause complications after a transplant. This targeted approach could potentially reduce the risk of graft-versus-host disease and improve transplant outcomes, offering a novel mechanism compared to traditional therapies.

What evidence suggests that venetoclax might be an effective treatment for transplant complications?

Research has shown that venetoclax may be beneficial when combined with hematopoietic cell transplantation for certain blood cancers. In this trial, participants will receive venetoclax alongside stem cell and kidney transplants. Studies have found that venetoclax, when used with other treatments, can help treat relapsed acute myeloid leukemia (AML) following stem cell transplants. This combination does not appear to increase the risk of transplant-related complications. Additionally, venetoclax has been used successfully in treatment plans without major safety concerns. While more information is needed, early results suggest that venetoclax could effectively manage transplant-related issues. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people aged 18-70 with certain blood cancers potentially curable by bone marrow or stem cell transplant and who also need a kidney transplant. They must be in good health, match specific lab criteria, have no active infections, and agree to birth control. Donors must be HLA-matched or haploidentical relatives.

Inclusion Criteria

Excellent health per pre-donor evaluation

Acceptable laboratory parameters, compatible ABO blood group

Negative donor lymphocyte cross match, no active viral infections

Exclusion Criteria

Participation in other investigational drug use at enrollment

Positivity for active HIV, HCV, or HBV infection

ABO blood group incompatibility in host-vs-graft direction

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax in addition to reduced intensity conditioning for HSC and kidney transplantation

1 week

Daily visits during treatment period

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Hematopoietic Cell Transplantation
• Hematopoietic Cell Transplantation Conditioning Regimen
• Venetoclax

Trial Overview

The trial tests the safety of adding Venetoclax to a reduced intensity conditioning regimen before combined hematopoietic stem cell (HSC) and kidney transplantation. It aims to achieve full donor hematopoiesis without severe toxicity from Venetoclax.

How Is the Trial Designed?

Group I: Recipient Experimental Treatment 4 Interventions

Stem Cell and Kidney Transplant

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12477258/

Clinical efficacy and safety of venetoclax combined with ... - PMC

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) cures 40–50% of high-risk AML patients (2), relapse remains the leading ...

2.

astctjournal.org

astctjournal.org/article/S2666-6367(25)00224-6/fulltext

Outcomes with Venetoclax and Hypomethylating Agents in ...

Our study analyzed the incidence of three common (grade III-IV) adverse events including neutropenia (73%, 95% CI 63-82%, I²=13%, p=0.33), thrombocytopenia (71% ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0006497124076900

Outcomes with Venetoclax and Hypomethylating Agents in ...

Venetoclax in combination with hypomethylating agents showed promising efficacy in the treatment of relapsed AML post-HSCT.

4.

ashpublications.org

ashpublications.org/ashclinicalnews/news/8514/A-Study-Evaluating-Safety-and-Efficacy-of

A Study Evaluating Safety and Efficacy of Venetoclax in ...

A study evaluating safety and efficacy of venetoclax in combination with azacitidine versus standard of care after allogeneic stem cell transplant.

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36318288/

Outcome after allogeneic hematopoietic stem cell ...

Our results showed that VEN-based regimen therapy followed by allo-HSCT in AML patients is feasible and does not increase the risk of transplant-related ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S000649711869411X

Safety and Efficacy of Adding Venetoclax to Reduced ...

Of the total 22 pts treated to date, 6 have died (5 from disease relapse and 1 from GVHD-related complications). Overall, 7 of 22 pts have ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41030254/

Clinical efficacy and safety of venetoclax combined with ...

Venetoclax in combination with HMAs provided superior clinical benefits over intensive chemotherapy in post-allo-HSCT AML relapse, ...

8.

ashpublications.org

ashpublications.org/blood/article/136/Supplement%201/11/472106/Venetoclax-Is-Safe-and-Tolerable-As-Post

Venetoclax Is Safe and Tolerable As Post-Transplant ...

Venetoclax is safe and tolerable as post-transplant maintenance therapy for AML patients at high risk for relapse.