NCT00293345

Brief Summary

This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
30

participants targeted

Target at P25-P50 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

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 16, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 17, 2006

Completed
3 months until next milestone

Study Start

First participant enrolled

June 1, 2006

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2012

Completed
Last Updated

September 30, 2013

Status Verified

September 1, 2013

Enrollment Period

6.3 years

First QC Date

February 16, 2006

Last Update Submit

September 27, 2013

Conditions

Anaplastic Large Cell LymphomaAngioimmunoblastic T-cell LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaPrimary Central Nervous System Hodgkin LymphomaPrimary Central Nervous System Non-Hodgkin LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaSmall Intestine LymphomaSplenic 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 Hodgkin LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary SyndromeStage 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 Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Cutaneous T-cell Non-Hodgkin 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 Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • MTD as assessed by the number of patients with dose-limiting toxicity (DLT)

    MTD is the maximum dose level with fewer than 2 of 3/6 patients experiencing DLT. The study uses standard method phase I design of dose escalation. DLT will be defined as greater or equal to Grade 3 non-hematologic or greater or equal to Grade 4 hematologic adverse event EXCEPT: greater or equal to Grade 3 nausea and greater or equal to Grade 3 vomiting that improves with antiemetic therapy; greater or equal to Grade 3 diarrhea that improves with Lomotil; and greater or equal to Grade 4 Neutropenia that recovers to less or equal to Grade 3 within 7 days of first identification.

    Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment

Secondary Outcomes (6)

  • Toxicity as assessed using the NCI Common Toxicity Criteria, Version 3.0

    Observed clinically for 4 hours after each 3-AP infusion during the first cycle of treatment and monitored until disease progression or for a maximum of 24 months following termination of treatment

  • Therapeutic response

    Tumor and radiologic measurements every 8 weeks from start of treatment. In addition to a baseline scan, confirmatory scans will also be obtained 8 weeks following initial documentation of an objective response.

  • Duration of overall response

    Baseline until disease progression or for a maximum of 24 months following termination of treatment.

  • Duration of stable disease

    Baseline until disease progression or for a maximum of 24 months following termination of treatment.

  • Levels of dCTP in PBMCs correlated to activity and toxicity of 3-AP

    PMBCs isolated immediately before and after 3-AP infusion (day 1), but before GEM is started on (day 2) on both course 1 and course 2 of treatment

  • +1 more secondary outcomes

Study Arms (1)

Treatment (gemcitabine hydrochloride, triapine)

EXPERIMENTAL

Patients receive 3-AP (Triapineî) IV over 24 hours followed by gemcitabine hydrochloride IV over 100-125 minutes on days 1 and 8. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: gemcitabine hydrochlorideDrug: triapine

Interventions

Also known as: dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar
Treatment (gemcitabine hydrochloride, triapine)
Also known as: 3-AP, OCX-191
Treatment (gemcitabine hydrochloride, triapine)

Eligibility Criteria

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

You may qualify if:

  • Histologically or cytologically confirmed advanced solid tumors or lymphoma
  • Disease considered incurable using standard treatment
  • ECOG performance status ≤ 2
  • Life expectancy \> 12 weeks
  • WBC ≥ 3,000/mm\^3
  • Absolute neutrophil count ≥ 1,500/mm\^3
  • Platelet count ≥ 100,000/mm\^3
  • Total bilirubin normal
  • AST/ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to and during study treatment
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to 3-AP (Triapine®) and/or gemcitabine hydrochloride
  • No known glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyIntraocular LymphomaLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom Macroglobulinemia

Interventions

Gemcitabine3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphadenopathyEye NeoplasmsNeoplasms by SiteLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemiaHematologic DiseasesLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Heterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Tanios Bekaii-Saab

    Ohio State University

    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

February 16, 2006

First Posted

February 17, 2006

Study Start

June 1, 2006

Primary Completion

October 1, 2012

Last Updated

September 30, 2013

Record last verified: 2013-09

Locations