Using vorinostat after stem cell transplant to prevent leukemia relapse in children

Epigenetic Modification for Relapse Prevention: a Dose-finding Study of Vorinostat Used in Combination With Low-dose Azacitidine in Children Undergoing Allogeneic Hematopoietic Cell Transplantation for Myeloid Malignancies

This study is testing if a new combination of medications can safely help children and teens who had a stem cell transplant for leukemia avoid a relapse of their disease.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 1 Year to 21 Years
• Sex: All
• Sponsor: Johns Hopkins All Children's Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, cyclophosphamide
• Locations: 1 site (Saint Petersburg, Florida)
• Trial ID: NCT03843528 on ClinicalTrials.gov

What this trial studies

This study evaluates the maximum tolerated dose of vorinostat when combined with low-dose azacitidine in children and adolescents aged 1 to 21 years who have undergone allogeneic hematopoietic cell transplantation for myeloid malignancies. Participants will initially receive standard azacitidine treatment, followed by vorinostat at varying doses based on their tolerance, using a dose-escalation approach. The goal is to determine the highest dose of vorinostat that can be safely administered without causing significant side effects while preventing relapse of the disease.

Who should consider this trial

Good fit: Ideal candidates are children and adolescents aged 1 to 21 years with a diagnosis of acute myeloid leukemia, myelodysplastic syndromes, mixed phenotype acute leukemia, or juvenile myelomonocytic leukemia who have undergone allogeneic hematopoietic cell transplantation.

Not a fit: Patients who are not undergoing allogeneic hematopoietic cell transplantation or those with other types of malignancies may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve relapse prevention in pediatric patients with myeloid malignancies post-transplant.

How similar studies have performed: While the combination of vorinostat and azacitidine has been explored in other contexts, this specific approach in pediatric patients post-transplant is novel.

Eligibility criteria

Inclusion Criteria:

1. Patient is 1 year to 21 years of age.
2. Patient has a diagnosis of AML, MDS, MDS/AML, MPAL, or JMML. Note: patients are allowed to have received a HMA or HDACi prior to undergoing alloHCT.
3. Patient has undergone allogeneic hematopoietic cell transplantation (no restrictions on conditioning regimen, donor or stem cell source, or GVHD prophylaxis regimen).
4. Patient and/or parent(s) or legal guardian(s) are capable of understanding the study, including potential benefits and risks, and sign written informed consent. Age-appropriate assent will be obtained.
5. Female patient of childbearing potential has a negative screening pregnancy test (urine or serum, as per local institutional standard).
6. Female patient with infant(s) agrees not to breastfeed her infant(s) while on study.
7. Patient of child-bearing potential (male and female) agrees to use effective method of contraception during the study.

Exclusion Criteria:

1. Patient is enrolled on a clinical trial with investigational post-transplant medications. Note: trials involving defibrotide, post-transplant cyclophosphamide, and Lactobacillus plantarum are permitted. Other trials involving investigational medications that aren't leukemia or GVHD-directed may also be permitted after consultation with the overall PI.
2. Patient has a planned administration of non-protocol chemotherapy, radiation therapy, donor leukocyte infusion, or immunotherapy during the planned study period.
3. Patient has a known allergy to azacitidine or vorinostat.
4. Patient has chronic myelogenous leukemia.
5. Concomitant use of coumarin-derived anticoagulants or valproic acid.

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Where this trial is running

Saint Petersburg, Florida

• Johns Hopkins All Children's Hospital — Saint Petersburg, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Cassandra Josephson, MD — Johns Hopkins All Children's Hospital
• Study coordinator: Benjamin Oshrine, MD

Conditions: Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia, Juvenile Myelomonocytic Leukemia