Hematologic DiseasesPhase 1/2NCT03842696
Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Allogeneic Blood and Marrow Transplantation
A Phase 1/2 study testing Vorinostat, Blood and Marrow Transplant (BMT) and Tacrolimus (or cyclosporine) in people with Hematologic Diseases and Acute Leukemia in Remission, run by University of Michigan Rogel Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to determine the recommended phase 2 dose of the drug Vorinostat in children, adolescents and young adults following allogeneic blood or marrow transplant (BMT) and determine whether the addition of Vorinostat to the standard graft versus host disease (GVHD) prophylaxis will reduce the… Read more about this study
- Who is it for?
- Ages 3 to 39 years
- Conditions the study is for
- Hematologic Diseases, Acute Leukemia in Remission, Chronic Myelogenous Leukemia - Chronic Phase
- What is being tested?
- Vorinostat, Blood and Marrow Transplant (BMT) and Tacrolimus (or cyclosporine)
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 7 sitesUnited States
- Study dates
- 4 Feb 2020to 1 Apr 2026
- Phase
- Phase 1/2
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 3 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- A prospective patient for allogeneic BMT for malignant hematologic conditions. A patient with history of CNS involvement is eligible if CNS disease is in remission at time of study consideration.
- The donor and recipient must have an HLA-match (8/8 HLA-A, -B, -C, and -DRB1) or haploidentical match (per protocol criteria). High resolution typing is required for all alleles.
- Diagnoses to be included:
- Acute Leukemia in remission. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, < 5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
- Chronic Myeologenous Leukemia (CML) in first or subsequent chronic phase failing to respond (or intolerant) to at least two different tyrosine kinase inhibitors. CML in accelerated or blast phase (CML-AP/BP) are eligible without requirement to fail tyrosine kinase inhibitor therapy, but must be in remission at time of enrollment. Remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment, <5% blasts in the bone marrow and absence of extramedullary disease including CNS involvement.
- Myelodysplastic syndrome (MDS) with intermediate or high-risk IPSS or equivalent IPSSR score with < 10% blasts in the bone marrow.
Show all 16Show fewer
- Mature B Cell Malignancies (including Mantle Cell Lymphoma, Follicular Lymphoma. Diffuse Large B Cell Lymphoma, Non-Hodgkin Lymphoma not otherwise specified).Subjects should have extinguished standard of care options prior to being considered eligible for this trial
- Subjects aged 3 to 39 years
- Lansky/Karnofsky Performance Scale score of 70% or higher
- Life expectancy of greater than 6 months
- Subjects must have normal organ and marrow function (as defined in protocol)
- Ability to take oral medication and be willing to adhere to the vorinostat regimen
- For females of reproductive potential and men: The effects of vorinostat on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitor agents as well as other therapeutic agents used in this trial (e.g., calcineurin inhibitor [tacrolimus or cyclosporine], methotrexate, mycophenolate, and cyclophosphamide) are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women must continue using contraceptives for at least 6 months after the end of therapy and men must continue contraceptive use for 3 months after completion of vorinostat administration.
- Ability to understand and the willingness to sign a written informed consent document
- Stated willingness to comply with all study procedures and availability for the duration of the Study
- For the cognitive assessment and patient-reported QOL exploratory correlative portion of the study, subjects and caregiver must speak, read and understand English. Subjects who are too young to read must be able to understand and speak English, age-appropriately. Subjects who do not speak, read and understand English but satisfy all other inclusion criteria may still participate in the study but will not complete the cognitive and QOL portions.
Who cannot join
- Subjects who are not a candidate for an allogeneic BMT based on the current local site institutional BMT program clinical practice guidelines. Organ function criteria will be utilized per the current local site institutional BMT program clinical practice guidelines. There will be no restriction to study entry based on hematological parameters.
- Presence of anti-donor HLA antibodies (per protocol criteria).
- Subjects who are enrolled on another GVHD treatment or prevention trial.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Subjects still under therapy for presumed or proven infection are eligible provided there is clear evidence (radiographic findings and/or culture results) that the infection is well-controlled. Subjects under treatment for infection will be enrolled only after clearance from the PI.
- Pregnant women are excluded from this study because vorinostat is a histone deacetylase inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with vorinostat, breastfeeding should be discontinued if the mother is treated with vorinostat. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Show all 11Show fewer
- Subjects with evidence of HIV seropositivity and/or positive PCR assay, HTLV1/HTLV2 seropositivity. The safety of allogeneic HSCT is not yet well-established for this population.
- Subjects with evidence of Hepatitis B or Hepatitis C PCR positivity. Hepatitis reactivation following myelosuppressive therapy can lead to fatal complications.
- Subjects with a history of prolonged QTc syndrome.
- Subjects who have had prior treatment with a drug like vorinostat (i.e., valproic acid) within the last 30 days.
- Subjects with documented evidence of cognitive impairment prior to enrollment on this study (diagnosis of dementia, mild cognitive impairment, or other neurological illnesses that impacts cognition) are excluded from the cognitive assessment portion of the study only.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
University of Colorado
Aurora, Colorado, 80045
Henry Ford Hospital
Detroit, Michigan, 48202
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Indianapolis, Indiana, 46202
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
About this study
Official title: A Phase 1/2 Multi-Center Trial of Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Allogeneic Blood and Marrow Transplantation
The purpose of this study is to determine the recommended phase 2 dose of the drug Vorinostat in children, adolescents and young adults following allogeneic blood or marrow transplant (BMT) and determine whether the addition of Vorinostat to the standard graft versus host disease (GVHD) prophylaxis will reduce the incidence of GVHD.
Read the detailed description
All subjects will undergo allogeneic blood or marrow transplant (BMT) according to local site institutional practice. The preparative regimen will depend upon the subject's underlying disease, type of transplant, previous therapy and comorbidities. Stem cells can be from donors of bone marrow or peripheral blood stem cells.
- Conditions
- Hematologic Diseases, Acute Leukemia in Remission, Chronic Myelogenous Leukemia - Chronic Phase, Chronic Myelogenous Leukemia, Accelerated Phase, Chronic Myelogenous Leukemia, Blastic Phase, Myelodysplastic Syndromes
- Being tested
- Vorinostat, Blood and Marrow Transplant (BMT), Tacrolimus (or cyclosporine), Methotrexate, Mycophenolate Mofetil (MMF)
- Keywords
- GVHD
- Medical subject headings
- Hematologic Diseases, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myeloid, Accelerated Phase, Blast Crisis, Myelodysplastic Syndromes, Lymphoma, Mantle-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
- HLA-matched BMT recipients: Vorinostat 30, 45 or 60 mg/m2 BID (100 mg/m2 BID maximum) PO from 10 days prior to transplant (day -10), until day +30 post-transplant.
- Haploidentical BMT recipients: Vorinostat 30, 45 or 60 mg/m2 BID (100 mg/m2 BID maximum) PO from 5 days after transplant (day +5), until day +30 post-transplant
Blood and Marrow Transplant (BMT)Procedure or surgery
Undergo allogeneic BMT according to local site institutional practice.
Tacrolimus (or cyclosporine)Drug
Tacrolimus (or cyclosporine if tacrolimus becomes in shortage during the study period) will begin on day -3. Intravenous or oral dosing is permitted.In the absence of GVHD, it is recommended that tacrolimus or cyclosporine tapering begin on day +100 post-transplant as per local site BMT program clinical practice guidelines. In the presence of GVHD, it is recommended that tacrolimus or cyclosporine be continued at therapeutic dosing.
MethotrexateDrug
HLA-matched BMT recipients: Methotrexate will be used in combination with tacrolimus (or cyclosporine) for standard GVHD prophylaxis. It will be given at a dose of 5 mg/m2/dose once daily intravenously on days +1, +3, +6, and +11. Standard criteria for administration will be followed per local site institutional BMT program clinical practice guidelines.
Mycophenolate Mofetil (MMF)Drug
Haploidentical BMT recipients: MMF will be used in combination with post-transplant cyclophosphamide and tacrolimus (or cyclosporine) for standard GVHD prophylaxis. MMF will start on day +5 and discontinue after the last dose on day +35 or may be continued if active GVHD is present. Given intravenously (preferred) or orally at a dose of 15 mg/kg/dose three times a day (based upon adjusted body weight) with the maximum total daily dose not to exceed 3 grams.
CyclophosphamideDrug
Haploidentical BMT recipients: Post-transplant cyclophosphamide (PT-Cy) will be used in combination with MMF and tacrolimus (or cyclosporine) for standard GVHD prophylaxis. PT-Cy (50 mg/kg/dose) given for two days, Days +3 and +4 after transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat | Experimental | Not described Receives: Drug: Vorinostat; Procedure: Blood and Marrow Transplant (BMT); Drug: Tacrolimus (or cyclosporine); Drug: Methotrexate; Drug: Mycophenolate Mofetil (MMF); Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1 portion: Determine the recommended phase 2 dose (RP2D) of the drug Vorinostat in children, adolescents, and young adults following allogeneic blood or marrow transplant (BMT).
Real time assessment of safety (DLTs), and pharmacokinetic (PK) and pharmacodynamics/histone acetylation (PD) analysis in each dose cohort prior to escalation of dose. Dose de/escalation will be determined using the 3+3 up-or-down algorithm.
Measured: At day +100
Phase 2 portion: Incidence of grade 2-4 acute GVHD within 100 days after transplant
Cumulative incidence will be determined using the proportional hazards method with a corresponding 95% confidence interval. GVHD severity will be determined clinically and graded by using the institutional BMT program clinical practice guidelines. (Pzrepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplantation 1995; 15:825-8.)
Measured: At day +100
Secondary outcomes (13)
Incidence of Grade 3-4 acute GVHD within 100 days after transplant
Cumulative incidence will be determined using the proportional hazards method with a corresponding 95% confidence interval. GVHD severity will be determined clinically and graded by using the institutional BMT program clinical practice guidelines. (Pzrepiorka D, Weisdorf D, Martin P, et al. Consensus conference on acute GVHD grading. Bone Marrow Transplantation 1995; 15:825-8.)
Measured: At day +100
Incidence of chronic GVHD
Measured: At 1 year
Incidence of relapse
Determined using the proportional hazards method with a corresponding 95% confidence interval.
Measured: At 1 year
Overall Survival
The Kaplan-Meier method will be used to estimate overall survival, measured from the date of transplantation to either death from any cause or end of follow-up.
Measured: At 1 year
Relapse-free Survival
Measured: At 1 year
GVHD-free relapse-free Survival
Measured: At 1 year
Number of participants with adverse events of grade 4 or higher that are probably or definitely related to vorinostat.
Graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Measured: Up to day +100
Percentage of participants with engraftment failure
Engraftment failure will be defined as the inability to achieve an absolute neutrophil count (ANC) > 500/uL within 28 days post-transplant.
Measured: Up to 28 days post-transplant
Percentage of participants for whom successful administration of at least 60% of the planned doses occurs between day -1 and day +30 post-transplant
Measured: Up to 30 days post-transplant
Maximum concentration (Cmax) of Vorinostat
Pharmacokinetic (PK) analysis will be performed using blood samples from subjects who have received at least one dose of vorinostat and for whom quantifiable PK samples are available. Pharmacokinetic variables will be summarized with descriptive statistics.
Measured: At day +1
Area under the curve (AUC) of Vorinostat
Measured: At day +1
Clearance (CL) of Vorinostat
Measured: At day +1
Volume (V) of Vorinostat
Measured: At day +1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2019
- Study start4 Feb 2020
- Primary completion30 Jul 2025
- Study completion1 Apr 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hematologic DiseasesStudies 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 1/2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Sponsor
- Investigators
- Sung W Choi, MD, MS, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03842696
- Sponsor's protocol ID
- UMCC 2018.081
- Other IDs
- HUM00147796, HUM00186659, UL1TR002240
- Status last verified
- Jan 2026
- First submitted
- 13 Feb 2019
- Last updated
- 27 Jan 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Parnell N, Cao X, Beumer JH, Braun TM, Cui Y, Fisher GJ, Hou G, Holleran J, Churay T, Rozwadowski M, Heider L, Vander Lugt MT, Kitko CL, Rahrig AL, Peres E, Williams KM, Talano JA, Fabrizio VA, Abusin G, Yanik GA, Magenau J, Riwes M, Geer MJ, Anand S, Ghosh M, Pawarode A, Votruba K, Reddy P, Choi SW. Vorinostat for graft-versus-host disease prevention in pediatric and young adult patients with hematologic malignancies. JCI Insight. 2026 Sep 24:e210272. doi: 10.1172/jci.insight.210272. Online ahead of print.
PubMed 42784255