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

ConditionGVHD
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age1-26
SponsorSung Won Choi

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Primary Immunodeficiency/Primary Immune regulatory disorders

Inborn errors of metabolism

Red blood cell disorders including hemoglobinopathies per protocol.

Inherited bone marrow failure syndromes

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

Treatment groups

55 Participants
are divided into 1 treatment group
Group A: VorinostatExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
1 year
2

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.

Time frame
By day+42 post-Hematopoietic stem cell transplant
3

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.

Time frame
Beyond day +42 post-HSCT
4

Secondary graft failure/rejection

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

Time frame
By day +42 post-HSCT

Secondary outcomes

1

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

This will be measured after HSCT.

Time frame
Day 100, 6-months, and 1-year post-HSCT
2

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

An event will be defined as death due to any cause, graft rejection/failure, or second transplant, whichever occurs first.

Time frame
1 year post-HSCT
3

Neutrophil engraftment at day 42

The time to engraftment of neutrophils \>500/microliter (μl) was defined as per Center for International Blood and Marrow Transplant Research (CIBMTR) standards, requiring donor chimerism for neutrophil engraftment.

Time frame
Day 42 post-HSCT
4

Platelet engraftment at day 100 post-HSCT

Platelet engraftment is defined as independence from platelet transfusion for at least 3 days with a platelet count of more than ≥20 × 10\^9/L.

Time frame
Day 100 post-HSCT

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sung Won Choi

Lead sponsor

University of Michigan

Sponsor institution

Source ClinicalTrials.gov
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