NCT00275080

Brief Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with decitabine in treating patients with advanced solid tumors or relapsed or refractory non-Hodgkin's lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, or chronic myelogenous leukemia. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with decitabine may kill more cancer cells.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
80

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2006

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

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

January 10, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 11, 2006

Completed
21 days until next milestone

Study Start

First participant enrolled

February 1, 2006

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2009

Completed
4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
Last Updated

August 27, 2014

Status Verified

June 1, 2014

Enrollment Period

3.8 years

First QC Date

January 10, 2006

Last Update Submit

August 26, 2014

Conditions

Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult 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)Blastic Phase Chronic Myelogenous LeukemiaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueNodal Marginal Zone B-cell LymphomaRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell 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 LymphomaSecondary Acute Myeloid LeukemiaSplenic Marginal Zone LymphomaStage 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 Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Small Lymphocytic 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 Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage 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 LymphomaUnspecified Adult Solid Tumor, Protocol SpecificUntreated Adult Acute Lymphoblastic LeukemiaUntreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose and recommended phase II dose of vorinostat and decitabine

    Graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

    Course 1

Secondary Outcomes (5)

  • Minimal effective dose of vorinostat in combination with decitabine by bone marrow and/or peripheral blood (for leukemia)

    Baseline and between days 3-10

  • Pharmacokinetics of vorinostat in conjunction with decitabine

    Days 1-15

  • Antitumor activity

    Every 4 weeks for leukemia and every 8 weeks for solid tumors or NHL

  • Methylation status of gene promoter regions and gene expression

    Baseline and between days 3-10

  • Altered response of leukemic cells to PPAr and RAR ligands

    Baseline and between days 3-8

Study Arms (1)

Treatment (enzyme inhibitor, chemotherapy)

EXPERIMENTAL

Regimen 1 (sequential dosing): Patients receive oral vorinostat two or three times daily on days 6-21 or days 6-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen 2 (concurrent dosing): Patients receive oral vorinostat two or three times daily on days 1-21, days 1-14 (patients with hematological malignancies only), or two times daily on days 1-12 (patients with solid tumors or NHL only) and decitabine IV over 1 hour on days 1-5.

Drug: vorinostatDrug: decitabine

Interventions

vorinostatDRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Treatment (enzyme inhibitor, chemotherapy)
decitabineDRUG

Given IV

Also known as: 5-aza-dCyd, 5AZA, DAC
Treatment (enzyme inhibitor, chemotherapy)

Eligibility Criteria

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

You may qualify if:

  • Diagnosis of 1 of the following:
  • Confirmed relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) or chronic myelogenous leukemia in blast crisis (CML-BC)
  • Patients with acute promyelocytic leukemia who have relapsed while on tretinoin allowed
  • Patients with previously untreated AML who refuse induction chemotherapy allowed
  • Patients who are not candidates for aggressive management (those that have medical conditions that prevent the administration of standard curative chemotherapy or those who require an allogeneic bone marrow transplantation for curative therapy but lack an appropriate donor) are allowed
  • Histologically or cytologically confirmed relapsed or refractory non-Hodgkin's lymphoma (NHL)
  • Histologically confirmed solid tumor that is metastatic or unresectable or for which standard curative or palliative measures do not exist or are no longer effective
  • Clinically or radiologically documented disease
  • Patients whose only evidence of disease is tumor marker elevation are not eligible
  • Patients with AML, ALL, or CML-BC who have cerebral spinal fluid involvement may be included
  • May be treated with intrathecal cytarabine and/or methotrexate prior to and/or during the study
  • No known brain metastases in patients with solid tumors or NHL
  • ECOG performance status 0-2
  • Karnofsky 60-100%
  • Life expectancy \> 12 weeks for patients with solid tumors (including non-Hodgkin's lymphoma) and 6 weeks for patients with hematological malignancies
  • +33 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Chedoke-McMaster Hospitals

Hamilton, Ontario, L8S 4L8, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Princess Margaret Hospital Phase 2 Consortium

Toronto, Ontario, M5G 2M9, Canada

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Congenital AbnormalitiesBlast CrisisLymphoma, B-Cell, Marginal ZonePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

VorinostatDecitabine

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and AbnormalitiesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveLeukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesMyeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellLymphomaLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, LymphoidEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, B-Cell

Intervention Hierarchy (Ancestors)

AnilidesAmidesOrganic ChemicalsAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsAzacitidineAza CompoundsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Officials

  • Karen Yee

    Princess Margaret Hospital Phase 2 Consortium

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 10, 2006

First Posted

January 11, 2006

Study Start

February 1, 2006

Primary Completion

November 1, 2009

Study Completion

August 1, 2014

Last Updated

August 27, 2014

Record last verified: 2014-06

Locations

CA(4)