Vorinostat for GVHD Prevention

Overseen By Tracey Churay

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Sung Won Choi

Must not be taking: Histone deacetylase inhibitors

Disqualifiers: Fanconi anemia, HIV, Hepatitis B, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5-6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called vorinostat, a histone deacetylase inhibitor, to determine its safety and effectiveness in preventing GVHD (graft-versus-host disease) in children and young adults undergoing bone marrow transplants. GVHD occurs when donor cells attack the recipient's body. The study targets individuals with non-cancerous conditions, such as certain immune disorders or metabolic issues, who require a transplant. Candidates with a non-cancerous condition needing a bone marrow transplant and who can take oral medication might be suitable for this trial. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any investigational therapies for your underlying disorder before enrolling, unless your doctor believes stopping them would be too risky. In that case, you must stop these therapies before starting the conditioning regimen.

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

Research shows that vorinostat is generally safe and well-tolerated for preventing graft-versus-host disease (GVHD). Studies have found that vorinostat, especially when combined with medications like tacrolimus and methotrexate, reduces cases of acute GVHD. As a result, fewer patients experience the severe reactions associated with this condition.

Additionally, vorinostat has shown positive safety results in similar situations. Patients typically handle the treatment well, with few reports of serious side effects. This is encouraging for its use in preventing GVHD in younger patients undergoing bone marrow transplants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GVHD?

Unlike standard treatments for graft-versus-host disease (GVHD), which often involve immunosuppressive drugs like corticosteroids, Vorinostat offers a novel approach. Researchers are excited about Vorinostat because it acts as a histone deacetylase inhibitor, which can modulate the immune response and potentially reduce the incidence and severity of GVHD. This treatment is also notable for its oral administration, making it more convenient compared to some existing therapies that require injections. By targeting the epigenetic regulation of immune cells, Vorinostat provides a unique mechanism that could enhance transplant outcomes without the side effects commonly associated with traditional immunosuppressive therapies.

What evidence suggests that vorinostat might be an effective treatment for GVHD?

Research has shown that vorinostat, the investigational treatment in this trial, may help prevent graft-versus-host disease (GVHD) when combined with other drugs like tacrolimus and methotrexate. Studies have found that patients who took vorinostat had a lower chance of developing GVHD compared to those who did not. For instance, one study reported that only 22% of patients who received vorinostat developed GVHD, which is much lower than usual rates. Another study also showed positive results, with 47% of patients not facing severe problems a year after treatment. These findings suggest that vorinostat could reduce the risk of GVHD in patients undergoing bone marrow transplants. ^{1 6 7 8 9}

Who Is on the Research Team?

Mark Vander Lugt, MD, MS

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for young individuals aged 1 to 26 with non-malignant disorders who are undergoing bone marrow transplant. It's designed to see if Vorinostat can prevent a common post-transplant complication called GVHD when combined with standard treatments.

Inclusion Criteria

Available donor per protocol (matched siblings and matched unrelated donors, haploidentical donors). The use of mismatched unrelated donors will not be allowed for this study

I agree to use two forms of birth control or remain abstinent as required.

Patient and/or legal guardian have signed the informed consent document

Exclusion Criteria

I was diagnosed with cancer in the last 5 years.

Seropositive for HIV or HTLV

I have active hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants undergo myeloablative conditioning prior to transplant

1-2 weeks

Treatment

Vorinostat is administered as GVHD prophylaxis from day -10 to day 30 post-transplant for matched sibling and unrelated donors, and from day +5 to day 30 for haploidentical donors

5-6 weeks

Follow-up

Participants are monitored for safety and effectiveness, including overall survival and event-free survival at various time points post-transplant

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Vorinostat

Trial Overview The study tests the safety and effectiveness of Vorinostat, an anti-inflammatory drug, as a preventive treatment for GVHD in adolescents and young adults receiving bone marrow transplants. Participants will receive Vorinostat along with other standard medications.

How Is the Trial Designed?

Group I: Vorinostat Experimental Treatment 1 Intervention

For matched sibling and matched unrelated donor transplant recipients Vorinostat will be given orally from day -10 to day 30 post-transplant. For Haploidentical donor transplant recipients Vorinostat will be given orally from day +5 (at least 24 hours after completion of the day +4 cyclophosphamide) through day 30 post-transplant. This will be given by liquid suspension or capsule by mouth.

Who Is Running the Clinical Trial?

Sung Won Choi

Lead Sponsor

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28784598/

Vorinostat plus tacrolimus/methotrexate to prevent GVHD ... Vorinostat is safe and results in low incidence of acute graft-versus-host disease (GVHD) after reduced-intensity conditioning, related donor hematopoietic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00810602?cond=%22Graft-Versus-Host%20Disease%22&intr=%22Vorinostat%22&viewType=Table&rank=3

Vorinostat to Prevent Graft Versus Host Disease Following ... A type of eligibility criteria that indicates whether people who do not have the condition/disease being studied can participate in that clinical study. ... An ...

3. ashpublications.org ashpublications.org/blood/article/130/15/1690/36400/Vorinostat-is-victorious-in-GVHD-prevention

Vorinostat is victorious in GVHD prevention - ASH Publications GRFS at 1 year was also encouraging at 47%, in comparison with 28% in the originally reported Minnesota adult cohort. ... Although histone ...

4. healio.com healio.com/news/hematology-oncology/20121210/addition-of-zolinza-to-hsct-conditioning-could-reduce-gvhd

Addition of Zolinza to HSCT conditioning could reduce GVHD Following treatment, patients who received vorinostat exhibited a significantly lower incidence of GVHD than their historical controls (22% vs.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4103793/

Phase 1/2 trial of vorinostat plus tacrolimus and ... Phase 1/2 trial of vorinostat plus tacrolimus and mycophenolate to prevent graft versus host disease following related donor reduced intensity conditioning ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00810602

NCT00810602 | Vorinostat to Prevent Graft Versus Host ... The goal of this study is to try to maximize the potential benefits, of giving patients less intense chemotherapy to reduce the toxic effects, letting the graft ...

7. ashpublications.org ashpublications.org/ashclinicalnews/news/3371/Examining-Vorinostat-to-Prevent-Graft-Versus-Host

Examining Vorinostat to Prevent Graft-Versus-Host Disease ... While the histone deacetylase (HDAC) inhibitor vorinostat led to a low incidence of acute graft-versus-host disease (GVHD) following hematopoietic cell ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204513705126

Vorinostat plus tacrolimus and mycophenolate to prevent ... We aimed to study the safety and activity of vorinostat, in combination with standard immunoprophylaxis, for prevention of GVHD in patients undergoing related- ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03842696

Study Details | NCT03842696 | Vorinostat for Graft vs Host ... The purpose of this study is to determine the recommended phase 2 dose of the drug Vorinostat in children, adolescents and young adults following allogeneic ...