Gene-Modified Tumor 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:	NCT00602121

Purpose

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

PURPOSE: This phase I/II trial is studying the side effects of autologous gene-modified tumor 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: immunoenzyme technique Procedure: laboratory biomarker analysis	Phase I Phase II

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

Drug Information available for: CD40 Ligand

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	PRIMAL: PROLONGED IMMUNISATION WITH AUTOLOGOUS CD40 LIGAND AND IL-2-EXPRESSING TUMOR CELLS FOR TREATMENT OF B-CHRONIC LYMPHOCYTIC LEUKEMIA (B-CLL)

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

Primary Outcome Measures:

Toxicity assessment as measured by NCI-CTCAE version 3.0 [ Designated as safety issue: Yes ]
Side population (SP) and non-SP B-cell chronic lymphocytic leukemia response [ Designated as safety issue: No ]
Immune response and antitumor assessment [ Designated as safety issue: No ]
Clinical response [ Designated as safety issue: No ]

Estimated Enrollment:	15
Study Start Date:	December 2006
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To determine the effects of prolonged immunization with CD40-ligand expressing and interleukin-2 secreting autologous B-cell chronic lymphocytic leukemia cells on the side population (SP) of tumor cells and on non-SP tumor cells.
To determine whether major histocompatibility complex-restricted or unrestricted antitumor immune responses are induced and sustained by the prolonged immunization.
To assess the safety of the prolonged vaccination schedule.

OUTLINE: Patients undergo peripheral blood collection and/or leukapheresis to obtain B-cell chronic lymphocytic leukemia (CLL) cells. B-cell 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 once weekly in weeks 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, and 28. Patients achieving a side population tumor cell response or clinical response receive additional vaccinations once weekly in weeks 32, 36, 40, 44, 48, and 52.

Blood is collected periodically to assess immune response as measured 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 and tumor side-population cells. When available, leukocytes are also assessed for the number of precursors reacting against autologous B-cell CLL cells using interferon-gamma ELISPOT assay. Plasma is tested for the presence of immunoglobulins against autologous B-cell CLL cells.

After completion of study treatment, patients are followed annually for 5 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of B-cell chronic lymphocytic leukemia (CLL)
Measurable disease
Manipulated B-cell CLL cells available (at least 12 injections)
No Richter transformation

PATIENT CHARACTERISTICS:

ECOG performance status of 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 ≤ 3 times ULN
Prothrombin time normal
Creatinine < 3 times normal for age or creatinine clearance > 80 mg/min
No active infection
No HIV positivity
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy
No congestive heart failure or significant arrhythmia
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 immunosuppressive drugs
No concurrent antibiotics except prophylactic trimethoprim sulfamethoxazole

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602121

Locations

United States, Texas
Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Vicky Torrano 832-824-7821
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Vicky Torrano 832-824-7821

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

Responsible Party:	Dan L. Duncan Cancer Center at Baylor College of Medicine ( Malcolm K. Brenner )
Study ID Numbers:	CDR0000582371, BCM-H-19747, BCM-PRIMAL
Study First Received:	January 24, 2008
Last Updated:	December 4, 2008
ClinicalTrials.gov Identifier:	NCT00602121
Health Authority:	Unspecified

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

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 14, 2009