NCT00224354

Brief Summary

In the laboratory, we will put a special gene into cancer cells that have been taken from the subject. This gene will make the cells produce interleukin 2 (IL-2), which may help the patient's immune system kill cancer cells. Also, we will use CD40 ligand (CD40L) with the IL-2. Studies of cancers in animals and in cancer cells that are grown in laboratories have suggested adding the CD40L helps the IL-2 work better. Some of these new cells will then be given back to the subject as a vaccine shot. We believe that a part of the subject's immune system (cells called T-reg cells) might try to kill off these special cells. If the T-reg cells do that, the vaccine would not work as well or last as long. To try to avoid this, before the special cells are put back into the subject's body, we will give them an intravenous (IV) dose of IL-2 immunotoxin (called denileuk diftitox or ONTAK). ONTAK should get rid of some of the T-reg cells in the subject's body which should help the special cells work better and longer. The purpose of this study is to learn the safety and cancer-fighting effects of using IL-2 with the vaccine.

Trial Health

15
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2005

Longer than P75 for phase_1

Status
withdrawn

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

Study Start

First participant enrolled

September 1, 2005

Completed
20 days until next milestone

First Submitted

Initial submission to the registry

September 21, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 23, 2005

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2009

Completed
Last Updated

May 21, 2012

Status Verified

May 1, 2012

Enrollment Period

4.3 years

First QC Date

September 21, 2005

Last Update Submit

May 18, 2012

Conditions

Keywords

LYMPHOCYTICB-LEUKEMIAB-CLL

Outcome Measures

Primary Outcomes (2)

  • Safety of (Treg) cells using interleukin-2 immunotoxin directed to the CD25 antigen in(B-CLL) patients, then six (SC) injections of autologous leukemic cells modified to secrete (hIL-2) and to express (hCD40L).

    15 years

  • To obtain preliminary data on the anti-tumor effects of this treatment regimen.

    15 years

Secondary Outcomes (1)

  • determine whether MHC-restricted or unrestricted anti-tumor immune responses are induced and sustained by the combination of Treg cell depletion and SC injections of B-CLL cells, which have been modified ex vivo to secrete hIL-2 and to express hCD40L

    15 years

Interventions

Patients will be treated with six subcutaneous injections of their IL-2-secreting and hCD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window

IL-2BIOLOGICAL

subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).

CD40LBIOLOGICAL

subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).

ONTAKDRUG

an interleukin-2 immunotoxin directed to the CD25 antigen (denileukin diftitox, ONTAK

Days 0, 2, and 4 (18 ug/kg) i.v

Also known as: ONTAK

Eligibility Criteria

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

You may qualify if:

  • Eligibility Criteria:
  • Manipulated B-CLL cells available (at least 6 injections)
  • B-CLL with measurable disease, not in Richter's transformation
  • Life expectancy greater than or equal to 10 weeks
  • ECOG 0-2 (see Section 4.3 of the full protocol for details)
  • Recovered from the toxic effects of all prior chemotherapy
  • Absolute neutrophil count (ANC) greater than or equal to 500/mL
  • Absolute lymphocyte count (ALC) greater than or equal to 200/mL
  • Hemoglobin greater than or equal to 8 g/dL
  • Platelet count greater than or equal to 50,000/mL
  • Total bilirubin less than or equal to 1.5mg/dL -SGOT less than or equal to 2 x Normal
  • Normal PTT -Creatinine less than 3 x Normal (age-related) or Creatinine clearance \> 80mg/min/1.73m2
  • Serum albumin level greater than or equal to 3 g/dl
  • Must not have received treatment with other investigational agents within the last 4 weeks
  • Practicing appropriate birth control during the study and for 3 months after the study is concluded.

You may not qualify if:

  • Congestive heart failure
  • Significant arrythmia or history of myocardial infarction
  • Active CNS disease or a history of seizure
  • Active infection / receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole
  • Seropositive for HIV
  • Pregnancy or lactation / will not use birth control methods
  • Autoimmune disease (GvHD, immune thrombocytopenia-ITP or autoimmune hemolytic anemia-AIHA)
  • Receiving immunosuppressive drugs
  • Hypersensitivity to denileukin diftitox or any of its components: diphteria toxin, interleukin-2, or excipients

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Interleukin-2CD40 Liganddenileukin diftitox

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

InterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological FactorsMembrane GlycoproteinsGlycoproteinsGlycoconjugatesCarbohydratesTumor Necrosis FactorsMembrane Proteins

Study Officials

  • GEORGE CARRUM, MD

    Baylor College of Medicine

    PRINCIPAL INVESTIGATOR
  • Malcolm K Brenner, MD

    Baylor College of Medicine

    STUDY DIRECTOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

September 21, 2005

First Posted

September 23, 2005

Study Start

September 1, 2005

Primary Completion

December 1, 2009

Study Completion

December 1, 2009

Last Updated

May 21, 2012

Record last verified: 2012-05