NCT01789255

Brief Summary

This pilot phase II trial studies how well giving vorinostat, tacrolimus, and methotrexate works in preventing graft-versus-host disease (GVHD) after stem cell transplant in patients with hematological malignancies. Vorinostat, tacrolimus, and methotrexate may be an effective treatment for GVHD caused by a bone marrow transplant.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jun 2013

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 7, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 12, 2013

Completed
4 months until next milestone

Study Start

First participant enrolled

June 1, 2013

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

November 13, 2015

Completed
Last Updated

July 24, 2018

Status Verified

June 1, 2018

Enrollment Period

9 months

First QC Date

February 7, 2013

Results QC Date

August 26, 2015

Last Update Submit

June 28, 2018

Conditions

Accelerated Phase Chronic Myelogenous LeukemiaAdult Acute Myeloid Leukemia in RemissionAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Grade III Lymphomatoid GranulomatosisB-cell Chronic Lymphocytic LeukemiaChronic Myelogenous Leukemia, BCR-ABL1 PositiveChronic Myelomonocytic LeukemiaChronic Phase Chronic Myelogenous LeukemiaContiguous Stage II Adult Burkitt LymphomaContiguous Stage II Adult Diffuse Large Cell LymphomaContiguous Stage II Adult Diffuse Mixed Cell LymphomaContiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaContiguous Stage II Adult Immunoblastic Large Cell LymphomaContiguous Stage II Adult Lymphoblastic LymphomaContiguous Stage II Grade 1 Follicular LymphomaContiguous Stage II Grade 2 Follicular LymphomaContiguous Stage II Grade 3 Follicular LymphomaContiguous Stage II Mantle Cell LymphomaContiguous Stage II Marginal Zone LymphomaContiguous Stage II Small Lymphocytic LymphomaCutaneous B-cell Non-Hodgkin LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueGraft Versus Host DiseaseIntraocular LymphomaMyelodysplastic Syndrome With Isolated Del(5q)Myelodysplastic/Myeloproliferative Neoplasm, UnclassifiableNodal Marginal Zone B-cell LymphomaNoncontiguous Stage II Adult Burkitt LymphomaNoncontiguous Stage II Adult Diffuse Large Cell LymphomaNoncontiguous Stage II Adult Diffuse Mixed Cell LymphomaNoncontiguous Stage II Adult Diffuse Small Cleaved Cell LymphomaNoncontiguous Stage II Adult Immunoblastic Large Cell LymphomaNoncontiguous Stage II Adult Lymphoblastic LymphomaNoncontiguous Stage II Grade 1 Follicular LymphomaNoncontiguous Stage II Grade 2 Follicular LymphomaNoncontiguous Stage II Grade 3 Follicular LymphomaNoncontiguous Stage II Mantle Cell LymphomaNoncontiguous Stage II Marginal Zone LymphomaNoncontiguous Stage II Small Lymphocytic LymphomaPost-transplant Lymphoproliferative DisorderPrimary Central Nervous System Hodgkin LymphomaPrimary Central Nervous System Non-Hodgkin LymphomaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRefractory AnemiaRefractory Anemia With Excess BlastsRefractory Anemia With Ringed SideroblastsRefractory Chronic Lymphocytic LeukemiaRefractory Cytopenia With Multilineage DysplasiaRefractory Hairy Cell LeukemiaRelapsing Chronic Myelogenous LeukemiaSecondary Central Nervous System Hodgkin LymphomaSecondary Central Nervous System Non-Hodgkin LymphomaSmall Intestine LymphomaSplenic Marginal Zone LymphomaStage I Adult Burkitt LymphomaStage I Adult Diffuse Large Cell LymphomaStage I Adult Diffuse Mixed Cell LymphomaStage I Adult Diffuse Small Cleaved Cell LymphomaStage I Adult Hodgkin LymphomaStage I Adult Immunoblastic Large Cell LymphomaStage I Adult Lymphoblastic LymphomaStage I Chronic Lymphocytic LeukemiaStage I Grade 1 Follicular LymphomaStage I Grade 2 Follicular LymphomaStage I Grade 3 Follicular LymphomaStage I Mantle Cell LymphomaStage I Marginal Zone LymphomaStage I Small Lymphocytic LymphomaStage II Adult Hodgkin LymphomaStage II Chronic Lymphocytic LeukemiaStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Hodgkin LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Chronic Lymphocytic LeukemiaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Small Lymphocytic LymphomaTesticular LymphomaWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • The Number of Participants That Experience Grade 2-4 Acute GVHD (Graft Versus Host Disease) by Day 100

    The incidence of grade 2-4 acute GVHD (Graft Versus Host Disease) by day 100 Grade 2 GVHD: Maculopapular rash covering 25-50% of BSA (Body Surface Area), bilirubin between 3.1-6 mg/dl, and/ or adult stool output between 1000-1500 ml/day (child between 20-30 ml/kg/day). Grade 3 GVHD: Maculopapular rash covering \>50% of BSA, bilirubin between 6.1-15 mg/dl, and/ or adult stool output \>1500 ml/day (child \>30 ml/kg/day). Grade 4 GVHD: Generalized erythroderma plus bullous formation and desquamation \>5% BSA, bilirubin \>15 mg/dl, and/ or severe abdominal pain with or without ileus, or grossly bloody stool.

    Day 100

Secondary Outcomes (6)

  • Mean Percent of Planned Dose Administered

    Up to day 30

  • The Percentage of Patients Alive Without GVHD or Use of Steroids

    Up to 1 year

  • The Percentage of Patients Alive at 1 Year

    Up to 1 year

  • The Percentage of Patients With Relapse at 1 Year

    Up to 1 year

  • Median Ac-H3 Levels in Patients Treated With Vorinostat and Patients Not Treated With Vorinostat

    Up to day 100

  • +1 more secondary outcomes

Study Arms (1)

Supportive care (vorinostat, tacrolimus, methotrexate)

EXPERIMENTAL

Patients receive vorinostat PO BID on days -10 to 100. Beginning on day -3, patients receive tacrolimus IV continuously or PO BID (or cyclosporine IV continuously or PO in patients unable to tolerate tacrolimus) with taper on days 100-180.Patients also receive methotrexate IV QD on days 1, 3, 6, and 11.

Drug: vorinostatDrug: tacrolimusDrug: cyclosporineDrug: methotrexateOther: laboratory biomarker analysisOther: pharmacological study

Interventions

vorinostatDRUG

Given PO

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Supportive care (vorinostat, tacrolimus, methotrexate)
tacrolimusDRUG

Given IV or PO

Also known as: FK 506, Prograf
Supportive care (vorinostat, tacrolimus, methotrexate)
cyclosporineDRUG

Given IV or PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Supportive care (vorinostat, tacrolimus, methotrexate)
methotrexateDRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX
Supportive care (vorinostat, tacrolimus, methotrexate)
laboratory biomarker analysisOTHER

Correlative studies

Supportive care (vorinostat, tacrolimus, methotrexate)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Supportive care (vorinostat, tacrolimus, methotrexate)

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A prospective patient for allogeneic HSCT for hematologic conditions, both malignant and non-malignant; donor can be unrelated marrow or peripheral blood cells; a patient with history of central nervous system (CNS) involvement is eligible if CNS disease is in remission at time of study consideration
  • The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and -DRB1; high-resolution typing is required for all alleles
  • Diagnoses to be included:
  • Acute myelogenous leukemia at the following stages:
  • First remission
  • Second or subsequent remission
  • Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and \< 5% blasts in the bone marrow
  • Chronic myelogenous leukemia at the following stages:
  • First or subsequent chronic phase:
  • Patient refused tyrosine kinase therapy or is otherwise not suited for it
  • Stable, not hematologic remission: blasts present in marrow and/or peripheral blood, but disease does not qualify as accelerated or blast phase
  • Hematologic remission: no blast cells or precursor cells in the blood or marrow
  • Partial cytogenetic remission: Philadelphia chromosome positive (Ph+) metaphases \> 0% but \< 35%
  • Complete cytogenetic remission: absence of Ph+ metaphases
  • Accelerated phase - any one of the following symptoms:
  • +46 more criteria

You may not qualify if:

  • Patients who are not a candidate for an unrelated donor allogeneic HSCT based on the current institutional bone marrow transplant (BMT) program clinical practice guidelines; organ function criteria will be utilized per the current institutional BMT program clinical practice guidelines; there will be no restriction to study entry based on hematological parameters
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
  • Patients undergoing a total body irradiation (TBI)-based conditioning regimen (TBI 1200 centigray \[cGy\])
  • 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; patients 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; patients under treatment for infection will be enrolled only after clearance from the Principal Investigator (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
  • Patients with evidence of human immunodeficiency virus (HIV) seropositivity and/or positive polymerase chain reaction (PCR) assay, human T-lymphotropic virus (HTLV)1/HTLV2 seropositivity; the safety of allogeneic HSCT is not yet well-established for this population
  • Patients with evidence of hepatitis B or hepatitis C PCR positivity; hepatitis reactivation following myelosuppressive therapy can lead to fatal complications
  • Patients with a history of prolonged corrected QT interval (QTc) syndrome
  • Patients asking or who have had prior treatment with a drug like vorinostat (i.e., valproic acid) within the last 30 days

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Michigan University Hospital

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated PhaseCongenital AbnormalitiesLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, Myelomonocytic, ChronicLeukemia, Myeloid, Chronic-PhaseGraft vs Host DiseaseIntraocular LymphomaChromosome 5q Deletion SyndromeMyeloproliferative DisordersLymphoma, B-Cell, Marginal ZoneLeukemia, Myeloid, AcuteBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellAnemia, RefractoryAnemia, Refractory, with Excess of BlastsLeukemia, Hairy CellWaldenstrom Macroglobulinemia

Interventions

VorinostatTacrolimusCyclosporineMethotrexatemerphos

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, B-CellLeukemia, LymphoidLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesMyelodysplastic-Myeloproliferative DiseasesLymphomaEye NeoplasmsNeoplasms by SiteLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsAnemiaMyelodysplastic SyndromesNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsMacrolidesLactonesCyclosporinsPeptides, CyclicMacrocyclic CompoundsPolycyclic CompoundsPeptidesAmino Acids, Peptides, and ProteinsAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Pavan Reddy, M.D.
Organization
University of Michigan Comprehensive Cancer Center
reddypr@umich.edu
734-647-5954

Study Officials

  • Pavan Reddy

    University of Michigan University Hospital

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
SUPPORTIVE CARE
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 7, 2013

First Posted

February 12, 2013

Study Start

June 1, 2013

Primary Completion

March 1, 2014

Study Completion

March 1, 2014

Last Updated

July 24, 2018

Results First Posted

November 13, 2015

Record last verified: 2018-06

Locations

US(1)