Clinical trial NCT00224354: Lymphocytic B-Leukemia (B-CLL) w/Human IL-2 Gene Modified & Human CD40 Ligand-Expressing Autologous Tumor Cells
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
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: CHRONIC LYMPHOCYTIC B-LEUKEMIA
Keywords: LYMPHOCYTIC
B-LEUKEMIA
B-CLL
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: The Methodist Hospital Research Institute
name: Center for Cell and Gene Therapy, Baylor College of Medicine
First posted: 2005-09-23
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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).
timeFrame: 15 years
measure: To obtain preliminary data on the anti-tumor effects of this treatment regimen.
timeFrame: 15 years
Secondary outcomes:
measure: 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
timeFrame: 15 years
Other outcomes:
Locations:
Study officials:
affiliation: Baylor College of Medicine
name: GEORGE CARRUM, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor College of Medicine
name: Malcolm K Brenner, MD
role: STUDY_DIRECTOR
References: