NCT00217412

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with isotretinoin in treating young patients with recurrent or refractory solid tumors, lymphoma, or leukemia. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Isotretinoin may cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving vorinostat together with isotretinoin may be an effective treatment for cancer.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Aug 2005

Longer than P75 for phase_1

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

Study Start

First participant enrolled

August 1, 2005

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 20, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 22, 2005

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
Last Updated

June 17, 2014

Status Verified

April 1, 2013

Enrollment Period

4.1 years

First QC Date

September 20, 2005

Last Update Submit

June 16, 2014

Conditions

Childhood Acute Promyelocytic Leukemia (M3)Childhood Atypical Teratoid/Rhabdoid TumorChildhood Burkitt LymphomaChildhood Chronic Myelogenous LeukemiaChildhood Diffuse Large Cell LymphomaChildhood Immunoblastic Large Cell LymphomaJuvenile Myelomonocytic LeukemiaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent Childhood Grade III Lymphomatoid GranulomatosisRecurrent Childhood Large Cell LymphomaRecurrent Childhood Lymphoblastic LymphomaRecurrent Childhood MedulloblastomaRecurrent Childhood Small Noncleaved Cell LymphomaRecurrent Childhood Supratentorial Primitive Neuroectodermal TumorRecurrent NeuroblastomaRecurrent/Refractory Childhood Hodgkin LymphomaRelapsing Chronic Myelogenous LeukemiaUnspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose (MTD) defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicities DLT graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

    28 days

Secondary Outcomes (1)

  • The proportion of patients who demonstrate each polymorphism

    Up to 4 years

Study Arms (3)

Arm I

EXPERIMENTAL

Group 1 (solid tumor or lymphoma patients): Patients receive oral SAHA once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients may be treated at the MTD.

Drug: vorinostat

Arm II

EXPERIMENTAL

Group 2 (leukemia patients): Patients receive SAHA as in group 1 at the MTD.

Drug: vorinostat

Arm III

EXPERIMENTAL

Group 3 (select solid tumor patients): Patients receive oral isotretinoin twice daily on days 1-14. Patients also receive SAHA once daily on days 1-28 OR once on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.The MTD of SAHA is determined as in group 1. An additional 6 patients may be treated at the MTD.

Drug: vorinostatDrug: isotretinoin

Interventions

vorinostatDRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Arm IArm IIArm III
isotretinoinDRUG

Given orally

Also known as: 13-CRA, Amnesteem, Cistane, Claravis, Sotret
Arm III

Eligibility Criteria

Age1 Year - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Histologically confirmed\* diagnosis of 1 of the following:
  • Recurrent or refractory solid tumor or lymphoma (for patients in group 1)
  • Measurable or evaluable disease
  • Recurrent or refractory leukemia (for patients in group 2)
  • Greater than 25% blasts in the bone marrow (i.e., M3 bone marrow)
  • Active extramedullary disease allowed except leptomeningeal disease
  • Recurrent or refractory CNS tumor of 1 of the following types (for patients in group 3):
  • Neuroblastoma
  • Medulloblastoma/CNS primitive neuroectodermal tumor
  • Atypical teratoid rhabdoid tumor
  • No known curative therapy or therapy proven to prolong survival with an acceptable quality of life exists
  • No bone marrow involvement by disease (for patients in groups 1 and 3)
  • No active CNS leukemia
  • Performance status - Lansky 50-100% (for patients ≤ 10 years of age)
  • Performance status - Karnofsky 60-100% (for patients \> 10 years of age)
  • +42 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Children's Oncology Group

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Rhabdoid TumorBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLeukemia, Myelomonocytic, JuvenilePrecursor Cell Lymphoblastic Leukemia-LymphomaDendritic Cell Sarcoma, InterdigitatingMedulloblastomaNeuroblastomaRecurrence

Interventions

VorinostatIsotretinoin

Condition Hierarchy (Ancestors)

Neoplasms, Complex and MixedNeoplasms by Histologic TypeNeoplasmsEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphomaLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, MyeloidLeukemiaMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesHematologic DiseasesLeukemia, LymphoidHistiocytic Disorders, MalignantHistiocytosisGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeuroectodermal Tumors, PrimitiveNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueNeuroectodermal Tumors, Primitive, PeripheralDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsRetinoidsCarotenoidsPolyenesAlkenesHydrocarbons, AcyclicHydrocarbonsCyclohexenesCyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicTerpenesPigments, BiologicalBiological Factors

Study Officials

  • Maryam Fouladi

    Children's Oncology Group

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 20, 2005

First Posted

September 22, 2005

Study Start

August 1, 2005

Primary Completion

September 1, 2009

Study Completion

September 1, 2009

Last Updated

June 17, 2014

Record last verified: 2013-04

Locations

US(1)