Acute Myeloid LeukemiaPhase 1NCT03843528
Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation
A Phase 1 study testing Vorinostat and Azacitidine Injection in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Johns Hopkins All Children's Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia
- What is being tested?
- Vorinostat and Azacitidine Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to 30 Oct 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
About this study
Official title: 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.
Read the 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:
- 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:
- To describe the dose-limiting toxicities (DLT) of the vorinostat used in combination with low-dose azacitidine.
- To describe rates of relapse, transplant related mortality, graft-versus-host disease, and overall survival.
- To describe the effect of epigenetic modification on lymphocyte reconstitution in the post-alloHCT setting.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia, Juvenile Myelomonocytic Leukemia
- Being tested
- Vorinostat, Azacitidine Injection
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Biphenotypic, Acute, Leukemia, Myelomonocytic, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
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.
Azacitidine InjectionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Vorinostat; Drug: Azacitidine Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 months
Secondary outcomes (5)
Dose-limiting toxicities
Rates of side effects from vorinostat will be recorded and described.
Measured: 4 months
GVHD
Incidence of GVHD will be recorded and described.
Measured: 1 year
Relapse
Incidence of relapse will be recorded and described
Measured: 1 year
Survival
Duration of survival will be recorded and described
Measured: 1 year
Immune recovery
Immune profile will be measured monthly for the first year post-transplant.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2019
- Study start1 May 2019
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 3+3 dose-escalation study
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins All Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cassandra Josephson, MD, Principal investigator, Johns Hopkins All Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03843528
- Sponsor's protocol ID
- IRB00202540
- Status last verified
- Jul 2026
- First submitted
- 24 Jan 2019
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03843528
- Acronym / sponsor ID
- IRB00202540
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Mixed Phenotype Acute Leukemia, Juvenile Myelomonocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Johns Hopkins All Children's HospitalUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Oct 2027 (estimated)
- First posted
- 18 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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:
- To describe the dose-limiting toxicities (DLT) of the vorinostat used in combination with low-dose azacitidine.
- To describe rates of relapse, transplant related mortality, graft-versus-host disease, and overall survival.
- To describe the effect of epigenetic modification on lymphocyte reconstitution in the post-alloHCT setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3+3 dose-escalation study
| Arm | Type | Receives |
|---|---|---|
| Combined therapy | Experimental | Drug: Vorinostat, Drug: Azacitidine InjectionPatients 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. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VorinostatVorinostat 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 | Combined therapy |
| Azacitidine InjectionAzacitidine 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. | Drug | Combined therapy |
Primary outcome
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.
5 secondary outcomes
Dose-limiting toxicities
Time frame: 4 months
GVHD
Time frame: 1 year
Relapse
Time frame: 1 year
Survival
Time frame: 1 year
Immune recovery
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cassandra Josephson, MD principal investigator
Johns Hopkins All Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat and Azacitidine Injection in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by Johns Hopkins All Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.