Vorinostat for Graft-versus-host Disease (GVHD) Prevention in Non-Malignant Adolescent and Young Adults (AYA) Population

NCT06995521 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: HUM00254327
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open label, phase 2 study to determine the safety and efficacy of vorinostat without serotherapy as GVHD prophylaxis when combined with either tacrolimus and methotrexate or post-transplant cyclophosphamide, tacrolimus, and mycophenolate in patients aged 1 to 26 years of age with non-malignant disorders undergoing bone marrow transplant following myeloablative conditioning.

Conditions

GVHD

Keywords

Non-malignant condition; Medication Vorinostat

Outcome Measures

Primary Outcomes (4)

• GVHD-free relapse-free Survival

  Composite endpoint of 1-year GVHD-free, event free survival (GEFS) with the addition of vorinostat to standard serotherapy-free GVHD prophylaxis. Grade III-IV acute GVHD and chronic GVHD requiring immunosuppression will be considered in this assessment. Events contributing to this endpoint will include death due to any cause, primary or secondary graft failure/rejection, or second HSCT, whichever occurs first.

  1 year

• Primary graft failure/rejection

  Defined as never achieving an absolute neutrophil count (ANC) ≥500/microliters (µL) or never achieving ≥5% donor myeloid chimerism assessed by peripheral blood chimerism assays by day +42 post-Hematopoietic stem cell transplant (HSCT). Second infusion of hematopoietic stem cells is also considered indicative of primary graft failure by day +42 post-HSCT.

  By day+42 post-Hematopoietic stem cell transplant

• Secondary graft failure/rejection

  Defined as \<5% donor myeloid chimerism in peripheral blood beyond day +42 post-HSCT in patients with prior documentation of hematopoietic recovery with ≥5% donor cells by day +42 post-HSCT.

  Beyond day +42 post-HSCT

• Secondary graft failure/rejection

  Second infusion of hematopoietic stem cells is also considered indicative of primary graft failure by day +42 post-HSCT

  By day +42 post-HSCT

Secondary Outcomes (11)

• Overall survival (OS) at day 100, 6-months, and 1-year post-HSCT

  Day 100, 6-months, and 1-year post-HSCT

• Event Free Survival (EFS) at 1-year post-HSCT

  1 year post-HSCT

• Neutrophil engraftment at day 42

  Day 42 post-HSCT

• Platelet engraftment at day 100 post-HSCT

  Day 100 post-HSCT

• Donor chimerism at day 28, 100, and 1-year post-HSCT

  Day 28, 100, and 1-year post-HSCT

Study Arms (1)

Vorinostat

EXPERIMENTAL

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.

Drug: Vorinostat

Interventions

Vorinostat DRUG

For Matched sibling and matched unrelated donor transplant recipients: Vorinostat will be given orally at a dose of 60 milligrams per square meter two times a day (BID) (120 mg/m2/day) from day -10 to day 30 post-transplant. The maximum dose will be 100 mg BID. Haploidentical donor transplant recipients: Vorinostat will be given orally at a dose of 60 mg/m2 BID (120 mg/m2/day) from day +5 (at least 24 hours after completion of the day +4 cyclophosphamide) through day 30 post-transplant. The maximum dose will be 100 mg BID. Dosing may be rounded by +/- 10%. Patients that are able to take capsules and whose calculated dose is ≥91 mg may take 100 mg capsules.

Also known as: Zolinza

Vorinostat

Eligibility Criteria

• Age: 1 Year - 26 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Non-malignant condition amenable to transplantation, including but not limited to:
• Primary Immunodeficiency/Primary Immune regulatory disorders
• Inborn errors of metabolism
• Red blood cell disorders including hemoglobinopathies per protocol.
• Inherited bone marrow failure syndromes
• 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.
• Patient and/or legal guardian have signed the informed consent document
• Adequate organ function and performance status for allogeneic hematopoietic stem cell transplantation as defined by institutional practice:
• Pulmonary Function: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in the first second (FEV1), Forced vital capacity (FVC) ≥50% predicted.
• Renal Function: Estimated or actual glomerular filtration rate (GFR) of ≥50 milliliters per minute (mL/min)/1.72 square meter (m2)
• Liver Function: aspartate aminotransferase (AST), alanine aminotransferase (ALT) \<3x upper limit of normal; total bilirubin ≤2.5 milligrams per deciliter (mg/dL) unless related to disease or Gilbert syndrome. There is no upper limit for bilirubin in patients with confirmed Gilbert syndrome.
• Cardiac Function: Ejection fraction (EF) ≥50% or fractional shortening (FS) ≥26%
• Performance Status: Karnofsky/Lansky score ≥70%(HIV) and Human T-lymphotropic virus type (HTLV) I/II negative
• Infectious Disease testing: human immunodeficiency virus
• Patients with transfusion-dependent anemias (per protocol) should have a liver MRI to document hepatic iron content (certain values will be excluded)

You may not qualify if:

• \- Previous diagnosis of Fanconi anemia, dyskeratosis congenita or other telomere biology disorders, inherited genetic conditions known to adversely affect DNA-repair, or other disorders with known chemo- or radiosensitivity.
• Additional testing may be conducted per investigator discretion but is not required for enrollment.
• Diagnosis of idiopathic severe aplastic anemia
• Diagnosis of severe combined immunodeficiency syndrome
• Diagnosis of malignancy within the last 5 years.
• Diagnosis of Epstein-Barr virus (EBV)-driven lymphoproliferative disorder within the last 5 years
• Uncontrolled bacterial, viral, or fungal infection at the time of enrollment
• Seropositive for HIV or HTLV
• Active hepatitis B or C
• Female patients that are pregnant or breast-feeding
• Inability to take oral medications.
• History of allergy to Vorinostat, related compounds, or any drugs used as part of the conditioning regimen or GVHD prophylaxis.
• Patients with transfusion-dependent anemia (≥8 packed red blood cell (PRBC) transfusions/year or ≥20 lifetime transfusions) that have a liver iron content of \>8 milligram (mg) Iron(Fe)/Gram dry weight or evidence of bridging fibrosis or cirrhosis on biopsy.
• Patients enrolled on another GVHD-prevention clinical trial.
• Patients receiving an ex-vivo T cell-depleted or cluster of differentiation (CD34)-selected stem cell graft.

Sponsors & Collaborators

• Sung Won Choi: lead

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Interventions

Vorinostat

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Mark Vander Lugt, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tracey Churay

CONTACT

734-615-1307; tchuray@med.umich.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 29, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)