Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation

July 14, 2026 updated by: Johns Hopkins All Children's Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Children and adolescents ages 1 to 21 years of age who are undergoing allogeneic hematopoietic cell transplantation for a myeloid malignancy (AML, MDS, JMML, MPAL) will be eligible. There are no restrictions on donor type, conditioning, stem cell source, of GVHD prophylaxis approach.

All participants will be treated on a single arm, and will initially receive 2 cycles of standard post-transplant azacitidine at a dose of 32mg/m2/dose IV/subcutnaeous for 5 days, in 28 day cycles. This is considered standard of care.

After tolerance of 2 cycles of azacitidine has been established, patients will be assigned to receive vorinostat orally at different dose levels, depending on the stage of the study. The dose level assignments will be conducted on a standard 3+3 design, whereby dose-escalation is peformed if previous patients tolerated the dose without dose-limiting toxicities, and dose-reduction is performed if dose-limiting toxicities are seen. The starting dose will be 100mg/m2/dose on days 1-7 and 15-21 of each 28 day cycles. This will be in addition to receiving azacitidine at the fixed dose above. In order to start each cycle, participants will be required to meet specific clinical parameters to ensure safety.

The dose of vorinostat between patients will be escalated or de-escalated until criteria for finding the maximum tolerated dose (MTD) is reached, and this will complete the study. Participants will continue to receive the prescribed dose of vorinostat for up to 7 cycles (9 total cycles of azacitidine).

Participants are followed for dose-limiting toxicities primarily during the first two course of combined therapy (cycles 3 and 4), but are continued to be tracked until the completion of all potential combined treatment (1 year or 7 combined cycles, whichever is earlier).

Principal aims:

1. To evaluate the maximum tolerated dose (MTD) of vorinostat used in combination with low-dose azacitidine after allogeneic hematopoietic cell transplantation (alloHCT) for childhood myeloid malignancies.

Secondary aims:

  1. To describe the dose-limiting toxicities (DLT) of the vorinostat used in combination with low-dose azacitidine.
  2. To describe rates of relapse, transplant related mortality, graft-versus-host disease, and overall survival.
  3. To describe the effect of epigenetic modification on lymphocyte reconstitution in the post-alloHCT setting.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Florida
      • St. Petersburg, Florida, United States, 33701
        • Johns Hopkins All Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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.

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Combined therapy

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
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.
Drug: Azacitidine Injection
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD)
Time Frame: 4 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Dose-limiting toxicities
Time Frame: 4 months
Rates of side effects from vorinostat will be recorded and described.
4 months
GVHD
Time Frame: 1 year
Incidence of GVHD will be recorded and described.
1 year
Relapse
Time Frame: 1 year
Incidence of relapse will be recorded and described
1 year
Survival
Time Frame: 1 year
Duration of survival will be recorded and described
1 year
Immune recovery
Time Frame: 1 year
Immune profile will be measured monthly for the first year post-transplant.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins All Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Cassandra Josephson, MD, Johns Hopkins All Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 24, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 14, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 18, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 15, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 14, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00202540

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings