Vorinostat in Preventing Graft Versus Host Disease in Children, Adolescents, and Young Adults Undergoing Blood and Bone Marrow Transplant

Active:	Yes
Cancer Type:	Cancer-Related Syndrome Hematopoietic Malignancies Leukemia Lymphoma Myelodysplastic Syndromes (MDS) Non-Hodgkin Lymphoma	NCT ID:	NCT03842696
Trial Phases:	Phase I Phase II	Protocol IDs:	UMCC 2018.081 (primary) NCI-2019-04695 HUM00147796
Eligibility:	3 - 21 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	University of Michigan Comprehensive Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT03842696

Summary

This phase I/II trial studies the side effects and best dose of vorinostat in preventing graft versus host disease in children, adolescents, and young adults who are undergoing unrelated donor blood and bone marrow transplant. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells, called graft-versus-host disease. During this process, chemicals (called cytokines) are released that may damage certain body tissues, including the gut, liver and skin. Vorinostat may be an effective treatment for graft-versus-host disease caused by a bone marrow transplant.

Objectives

PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) of vorinostat in children, adolescents and young adults following allogeneic hematopoietic cell transplantation (HCT). (Part A)
II. To determine the incidence of grade 2-4 acute graft versus host disease (GVHD) by day 100 in subjects who receive vorinostat in addition to standard GVHD prophylaxis after allogeneic bone marrow transplant (BMT). (Part B)

SECONDARY OBJECTIVES:
I. To confirm the pharmacokinetics (PK) of vorinostat and demonstrate safety and feasibility of vorinostat for GVHD prophylaxis in BMT subjects aged 3-21.
II. Determine the incidence of severe grade 3-4 acute GVHD at day +100, and chronic GVHD, relapse and 1-year survival in vorinostat-treated children, adolescents and young adults.

EXPLORATORY OBJECTIVES:
I. To correlate laboratory studies and patient outcomes after histone deacetylase (HDAC) inhibition.
II. To correlate patient cognitive function and patient-reported quality of life (QOL) outcomes with clinical outcomes.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) twice daily (BID) on days -10 to 100. Patients may receive fludarabine intravenously (IV) over 30 minutes on days -9 to -6 or -6 to -2, melphalan IV over 30 minutes on days -3 to -2, or busulfan IV over 2 hours or PO on days -5 to -2. Patients also receive tacrolimus IV continuously or PO BID starting on day -3 and taper beginning on day 100 post transplant. Patients then undergo BMT on day 0 and receive methotrexate IV once daily (QD) on days 1, 3, 6, and 11 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 9 months and 1 year.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

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