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
18 Years
N/A
Both
CHRONIC LYMPHOCYTIC B-LEUKEMIA
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome 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).
Outcome Time Frame:
15 years
Safety Issue:
Yes
Principal Investigator
GEORGE CARRUM, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Baylor College of Medicine
Authority:
United States: Food and Drug Administration
Study ID:
17656
NCT ID:
NCT00224354
Start Date:
September 2005
Completion Date:
December 2009
Related Keywords:
- Chronic Lymphocytic B-Leukemia
- LYMPHOCYTIC
- B-LEUKEMIA
- B-CLL
- Leukemia
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