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

Sponsors and Collaborators:	Baylor College of Medicine The Methodist Hospital System Center for Cell and Gene Therapy
Information provided by:	Baylor College of Medicine
ClinicalTrials.gov Identifier:	NCT00224354

Purpose

The purpose of this study is to learn the safety and cancer-fighting effects of using IL-2 with the vaccines ("shots") made for you.

Condition	Intervention	Phase
Chronic Lymphocytic B-Leukemia B-CLL	Biological: IL-2 secreting and hCL4OL-expressing autologous B-CLL cells Biological: IL-2 Biological: CD40L Drug: ONTAK Biological: immunotoxin dose	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Interleukin-2 Denileukin diftitox CD40 Ligand

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

Further study details as provided by Baylor College of Medicine:

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). [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
To obtain preliminary data on the anti-tumor effects of this treatment regimen. [ Time Frame: 15 years ] [ Designated as safety issue: No ]

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 [ Time Frame: 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	12
Study Start Date:	September 2005
Estimated Study Completion Date:	December 2024
Estimated Primary Completion Date:	December 2024 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00224354

Contacts

Contact: GEORGE CARRUM, MD

713-394-6250

gcarrum@bcm.tmc.edu

Locations

United States, Texas
The Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD 713-394-6250 gcarrum@bcm.tmc.edu

Sponsors and Collaborators

Baylor College of Medicine

The Methodist Hospital System

Center for Cell and Gene Therapy

Investigators

Principal Investigator:	GEORGE CARRUM, MD	Baylor College of Medicine
Study Director:	Malcolm K Brenner, MD	Baylor College of Medicine

More Information

Responsible Party:	Baylor College of Medicine ( Malcolm Brenner, MD )
Study ID Numbers:	17656, CLONTAK
Study First Received:	September 21, 2005
Last Updated:	December 20, 2007
ClinicalTrials.gov Identifier:	NCT00224354
Health Authority:	United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:

LYMPHOCYTIC
B-LEUKEMIA
B-CLL

Study placed in the following topic categories:

Leukemia
Interleukin-2
Denileukin diftitox
Immunotoxins

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Sensory System Agents
Analgesics, Non-Narcotic
Antineoplastic Agents

Therapeutic Uses
Physiological Effects of Drugs
Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009