Gene-Modified Cancer Cells in Treating Patients With B-Cell Chronic Lymphocytic Leukemia - Full Text View

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00609076

Purpose

RATIONALE: Vaccines made from a patient's gene-modified cancer cells may help the body build an effective immune response to kill cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified cancer cells and to see how well it works in treating patients with B-cell chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: autologous tumor cell vaccine Procedure: biopsy Procedure: immunoenzyme technique Procedure: laboratory biomarker analysis	Phase I

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

Drug Information available for: Interleukin-2 CD40 Ligand

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	TREATMENT OF CHRONIC LYMPHOCYTIC B-LEUKEMIA (B-CLL) WITH HUMAN IL-2 GENE MODIFIED AND HUMAN CD40 LIGAND-EXPRESSING AUTOLOGOUS TUMOR CELLS

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Qualitative and quantitative toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determination of immunologic efficacy [ Designated as safety issue: No ]
Antitumor effects [ Designated as safety issue: No ]

Estimated Enrollment:	21
Study Start Date:	July 2002
Estimated Primary Completion Date:	December 2022 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To determine the safety of autologous malignant B cells from patients with chronic lymphocytic leukemia (B-CLL), which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).
To determine whether major histocompatability complex-restricted or unrestricted antitumor immune responses are induced by subcutaneous injections of B-CLL cells, which have been modified ex vivo to secrete hIL-2 and to express hCD40L.
To obtain preliminary data on the antitumor effects of this treatment regimen.

OUTLINE: This is a dose-escalation study of CD40-ligand-expressing B-cell chronic lymphocytic leukemia (B-CLL) cells.

Patients undergo peripheral blood and/or leukapheresis for collection of B-CLL cells. B-CLL cells are isolated and transduced by the human interleukin-2 (IL-2) adenoviral vector and stimulated with CD40-ligand for the production of CD40-ligand-expressing and IL-2 gene-modified autologous tumor cells.

Patients receive CD40-ligand-expressing and IL-2 gene-modified autologous tumor cell vaccine subcutaneously (SC) once weekly in weeks 1, 2, and 3. Patients with stable or responding disease receive 3 additional injections on weeks 4, 6, and 8 in the absence of disease progression or unacceptable toxicity.

After a 3-4 week rest, patients are re-evaluated for toxicity and response. Patients with disease regression after the administration of 6 injections, may receive additional vaccinations once weekly at 2-week intervals.

Blood samples are collected once weekly for 10 weeks, in week 12, monthly for 1 year, and annually thereafter for 15 years for immune analysis. Samples are analyzed for immune response by numeric and phenotypical characterization of circulating leukocyte sub-populations, including analysis of CD4+, CD8+ and CD25+ T-lymphocytes, and CD16+ and CD56+ NK cells; the number of precursors reacting against autologous B-CLL cells using IFN-gamma ELISPOT assay; and the presence of immunoglobulins against autologous B-CLL cells in plasma. Tumor response is analyzed via bone marrow samples and skin punch biopsies.

After completion of study treatment, patients are followed monthly for 1 year, and then annually for 15 years.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia
- No Richter's transformation (e.g., aggressive non-Hodgkin lymphoma)
Measurable or nonmeasurable disease
Untreated patients or patients in complete remission are enrolled for vaccine administration in a therapeutic (i.e., no chemotherapy) window of three months during which the patient may not present with rapid clinical progression
- Vaccine production for patients in complete remission can only be achieved if tumor cells have been collected before entering complete remission

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 10 weeks
Absolute neutrophil count ≥ 500/µL
Absolute lymphocyte count ≥ 200/μL
Platelet count ≥ 50,000/μL
Hemoglobin ≥ 8 g/dL
Total bilirubin ≤ 1.5 mg/dL
SGOT ≤ 2 times normal
PTT normal
Creatinine < 3 times normal for age or creatinine clearance > 80 mL/min
No active infection
No HIV positivity
Not pregnant or nursing
Fertile patients must use effective contraception during and for 3 months after completion of study treatment
No autoimmune disease, including any of the following:
- Active graft-versus-host disease
- Refractory immune thrombocytopenia
- Refractory autoimmune hemolytic anemia

PRIOR CONCURRENT THERAPY:

Recovered from toxic effects of all prior chemotherapy
More than 4 weeks since prior investigational agents
No concurrent antibiotics (except prophylactic trimethoprim sulfamethoxazole)
No concurrent immunosuppressive drugs
No concurrent cytotoxic therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00609076

Locations

United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
Houston, Texas, United States, 77030-2399

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Study Chair:

Malcolm K. Brenner, MD, PhD

Baylor College of Medicine

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000582397, BCM-H-11541, BCM-CLIMAT
Study First Received:	January 30, 2008
Last Updated:	October 8, 2008
ClinicalTrials.gov Identifier:	NCT00609076
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

B-cell chronic lymphocytic leukemia
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia

stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Lymphatic Diseases
Leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders

Interleukin-2
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, chronic
Lymphoproliferative Disorders
Leukemia, B-Cell

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009