search
Back to results

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

Primary Purpose

CHRONIC LYMPHOCYTIC B-LEUKEMIA

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
IL-2 secreting and hCL4OL-expressing autologous B-CLL cells
IL-2
CD40L
ONTAK
immunotoxin dose
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for CHRONIC LYMPHOCYTIC B-LEUKEMIA focused on measuring LYMPHOCYTIC, B-LEUKEMIA, B-CLL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Outcomes

    Primary Outcome Measures

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

    Secondary Outcome Measures

    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

    Full Information

    First Posted
    September 21, 2005
    Last Updated
    May 18, 2012
    Sponsor
    Baylor College of Medicine
    Collaborators
    The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00224354
    Brief Title
    Lymphocytic B-Leukemia (B-CLL) w/Human IL-2 Gene Modified & Human CD40 Ligand-Expressing Autologous Tumor Cells
    Acronym
    CLONTAK
    Official Title
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2012
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    September 2005 (undefined)
    Primary Completion Date
    December 2009 (Actual)
    Study Completion Date
    December 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Baylor College of Medicine
    Collaborators
    The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    CHRONIC LYMPHOCYTIC B-LEUKEMIA
    Keywords
    LYMPHOCYTIC, B-LEUKEMIA, B-CLL

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Biological
    Intervention Name(s)
    IL-2 secreting and hCL4OL-expressing autologous B-CLL cells
    Intervention Description
    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
    Intervention Type
    Biological
    Intervention Name(s)
    IL-2
    Intervention Description
    subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
    Intervention Type
    Biological
    Intervention Name(s)
    CD40L
    Intervention Description
    subcutaneous (SC) injections of autologous leukemic cells modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
    Intervention Type
    Drug
    Intervention Name(s)
    ONTAK
    Intervention Description
    an interleukin-2 immunotoxin directed to the CD25 antigen (denileukin diftitox, ONTAK
    Intervention Type
    Biological
    Intervention Name(s)
    immunotoxin dose
    Other Intervention Name(s)
    ONTAK
    Intervention Description
    Days 0, 2, and 4 (18 ug/kg) i.v
    Primary Outcome Measure Information:
    Title
    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
    Title
    To obtain preliminary data on the anti-tumor effects of this treatment regimen.
    Time Frame
    15 years
    Secondary Outcome Measure Information:
    Title
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    GEORGE CARRUM, MD
    Organizational Affiliation
    Baylor College of Medicine
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Malcolm K Brenner, MD
    Organizational Affiliation
    Baylor College of Medicine
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs