Lymphocytic B-Leukemia (B-CLL) w/Human IL-2 Gene Modified & Human CD40 Ligand-Expressing Autologous Tumor Cells (CLONTAK)

May 18, 2012 updated by: George Carrum, Baylor College of Medicine

Treatment of Chronic Lymphocytic B-Leukemia (B-CLL) With Human IL-2 Gene Modified and Human CD40 Ligand-Expressing Autologous Tumor Cells After Depletion of Regulatory T Cells

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This is a phase I trial to assess the safety of depleting regulatory T (Treg) cells using 1-3 doses of an interleukin-2 immunotoxin directed to the CD25 antigen (denileukin diftitox, ONTAK) in chronic lymphocytic leukemia (B-CLL) patients, followed by six subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L). Patients will receive a fixed dose (2 x 10e7) of IL-2 secreting B-cells together with 2 x 10e7 hCD40L expressing B-cells, representing a safe, well tolerated and immunogenic dose in our previous dose escalation study.

All eligible patients will be treated with six injections. Any patient whose disease regresses after the administration of 6 injections may be offered further injections of tumor vaccine if sufficient vaccine is available. There will be no use of placebo or control subjects.

Study Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pre Inclusion Eligibility Criteria: Proof of B-CLL diagnosis not in Richter's transformation

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.

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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).
Time Frame: 15 years
15 years
To obtain preliminary data on the anti-tumor effects of this treatment regimen.
Time Frame: 15 years
15 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: 15 years
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baylor College of Medicine

Collaborators

The Methodist Hospital Research Institute
Center for Cell and Gene Therapy, Baylor College of Medicine

Investigators

  • Principal Investigator: George Carrum, MD, Baylor College of Medicine
  • Study Director: Malcolm K Brenner, MD, Baylor College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

September 21, 2005

First Submitted That Met QC Criteria

September 21, 2005

First Posted (Estimate)

September 23, 2005

Study Record Updates

Last Update Posted (Estimate)

May 21, 2012

Last Update Submitted That Met QC Criteria

May 18, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17656
  • CLONTAK

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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