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

NCT ID: NCT06995521

Last Updated: 2025-10-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-06-30

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.

Detailed Description

The Hypothesis of the trial:

The addition of vorinostat to standard GVHD prophylaxis without serotherapy will lead to improved GVHD-free event-free survival (GEFS) at 1-year post-transplant compared to historical serotherapy-containing GVHD prophylaxis regimens in patients with non-malignant disorders (NMD) undergoing Hematopoietic stem cell transplant (HSCT).

Conditions

GVHD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vorinostat

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.

Group Type: EXPERIMENTAL

Vorinostat

Intervention Type: 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.

Interventions

Vorinostat

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.

Intervention Type: DRUG

Other Intervention Names

Zolinza

Eligibility Criteria

Inclusion Criteria

• Non-malignant condition amenable to transplantation, including but not limited to:

1. Primary Immunodeficiency/Primary Immune regulatory disorders

2. Inborn errors of metabolism

3. Red blood cell disorders including hemoglobinopathies per protocol.

4. 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:

1. 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.

2. Renal Function: Estimated or actual glomerular filtration rate (GFR) of ≥50 milliliters per minute (mL/min)/1.72 square meter (m2)

3. 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.

4. Cardiac Function: Ejection fraction (EF) ≥50% or fractional shortening (FS) ≥26%

5. Performance Status: Karnofsky/Lansky score ≥70%(HIV) and Human T-lymphotropic virus type (HTLV) I/II negative

6. 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)
• All patients of childbearing age must agree to practice 2 effective methods of contraception at the same time or agree to abstinence for 6 months after the last dose for females. Males with female sexual partners of reproductive potential should use contraception during treatment and for at least 3 months after the last dose.
• Patients treated with other investigational therapies for underlying disorder must discontinue these therapies prior to enrollment on the study unless, in the opinion of the treating physician, discontinuing these therapies prior to transplant would place the patient at undue risk of morbidity or mortality. In this case, patients must discontinue investigational therapies prior to initiation of the conditioning regimen.

Exclusion Criteria

• 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.
• Subjects that have had prior treatment with a histone deacetylase inhibitor (e.g. vorinostat, valproic acid) within the last 30 days.
• History of prolonged corrected QT interval (QTc) syndrome.
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 26 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sung Won Choi

OTHER

Sponsor Role: lead

Responsible Party

Sung Won Choi

Professor of Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mark Vander Lugt, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Central Contacts

Tracey Churay

Role: CONTACT

tchuray@med.umich.edu

734-615-1307

Facility Contacts

Tracey Churay

Role: primary

tchuray@med.umich.edu

734-615-1307

Other Identifiers

HUM00254327

Identifier Type: -

Identifier Source: org_study_id