Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation

NCT03843528 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB00202540
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to evaluate the maximum tolerated (MTD) of vorinostat used in combination with low-dose azacitidine after allogeneic hematopoietic cell transplantation (alloHCT) for prevention of relapse of childhood myeloid malignancies.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes; Mixed Phenotype Acute Leukemia; Juvenile Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  The primary outcome of this study is to determine the MTD of vorinostat in combination with low-dose azacitidine, using dose-escalation methodology. This is based on toxicities developed by participants enrolled on the study.

  4 months

Secondary Outcomes (5)

• Dose-limiting toxicities

  4 months

• GVHD

  1 year

• Relapse

  1 year

• Survival

  1 year

• Immune recovery

  1 year

Study Arms (1)

Combined therapy

EXPERIMENTAL

Patients will be enrolled in blocks of 3, with vorinostat dose-escalation according to 3+3 study design. Low-dose azacitidine will be administered in a fixed dose to all patients, for days 1-5 of each 28 day cycle.

Drug: Vorinostat; Drug: Azacitidine Injection

Interventions

Vorinostat DRUG

Vorinostat will be administered concurrent with low-dose azacitidine post-transplant, on days 1-7 and 15-21 of 28 day cycles. This is an oral medication.

Combined therapy

Azacitidine Injection DRUG

Azacitidine will be administered on days 1-5 of each 28 day cycle, either by IV or subcutaneous injection. The dose of azacitidine will be fixed, with no dose-escalation.

Combined therapy

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patient is 1 year to 21 years of age.
• 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.
• Patient has undergone allogeneic hematopoietic cell transplantation (no restrictions on conditioning regimen, donor or stem cell source, or GVHD prophylaxis regimen).
• 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.
• Female patient of childbearing potential has a negative screening pregnancy test (urine or serum, as per local institutional standard).
• Female patient with infant(s) agrees not to breastfeed her infant(s) while on study.
• Patient of child-bearing potential (male and female) agrees to use effective method of contraception during the study.

You may not qualify if:

• 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.
• Patient has a planned administration of non-protocol chemotherapy, radiation therapy, donor leukocyte infusion, or immunotherapy during the planned study period.
• Patient has a known allergy to azacitidine or vorinostat.
• Patient has chronic myelogenous leukemia.
• Concomitant use of coumarin-derived anticoagulants or valproic acid.

Sponsors & Collaborators

• Johns Hopkins All Children's Hospital: lead

Study Sites (1)

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Biphenotypic, Acute; Leukemia, Myelomonocytic, Juvenile

Interventions

Vorinostat; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Cassandra Josephson, MD

  Johns Hopkins All Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3+3 dose-escalation study

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: February 18, 2019
• Study Start: May 1, 2019
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)