Treatment of Chronic Lymphocytic B-Leukemia With IL-2 and CD-40 Autologous Tumor Cells

NCT00058786 | Completed Phase 1 DMC

• 2 other identifiers: H11541Climat
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to determine the safety and dosage of special cells that may make the patients own immune system fight the cancer. To do this, we will put a special gene into cancer cells that have been taken from the patient. This will be done in the laboratory. This gene will make the cells produce interleukin 2 (IL-2), which is a natural substance that may help the immune system kill cancer cells. Additionally, we will stimulate the cancer cells with another natural protein called CD40 ligand (CD40L), which preclinical human and animal studies suggest will help IL-2 perform better. Some of these cells will then be put back into the body. The cells are grown with normal embryonic fibroblasts. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that combining substances like IL-2 and CD40L helps the body kill cancer cells. The purpose of this study is to learn the side effects and the safest effective dose of these special cells on the disease

Conditions

Chronic Lymphocytic B-Leukemia

Outcome Measures

Primary Outcomes (1)

• Safety of 3-6 SQ injections of autologous malignant B cells from chronic B-CLL pts, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L).

  3 mths

Secondary Outcomes (2)

• To determine whether MHC- restricted or unrestricted anti-tumor immune responses are induced by SC injections of B-CLL cells which have been modified ex vivo to secrete hIL-2 and to express hCD40L

  15 yrs

• To obtain preliminary data on the anti-tumor effects of this treatment regimen

  15 yrs

Interventions

Injection of IL-2-secreting CD40L-expressing autologous B-CLL cells BIOLOGICAL

Patients may be treated with a minimum of three up to six injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window, i.e. in the absence of concurrent cytotoxic therapy. Any patient whose disease regresses after the administration of 6 injections may be offered further injections (i.e. more than 6 injections) of tumor vaccine at the dose level previously administered, if enough vaccines are available. Patients will receive a fixed dose of IL-2 secreting B-CLL cells throughout the entire treatment protocol (see Section 5.8), determined by previous studies in acute leukemia and in neuroblastoma, in which this level of IL-2 production has been safe. The dose escalation of CD40L-expressing cells is designed to reach the IL2/CD40L ratio shown to be effective in our preclinical models of neuroblastoma and lymphoma.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richter's transformation) with (group A) or without (group B) measurable disease. Untreated or complete remission patients will be enrolled for vaccine administration in a therapeutic (i.e. no chemotherapy) window of three months. If during these three months (necessary to complete the vaccine study) the patient presents with rapid clinical progression, he or she will be excluded from our current study and will receive treatment according to the standard institutional guidelines. IMPORTANT NOTE: Vaccine production for complete remission patients can only be achieved if tumor cells have been collected BEFORE entering complete remission.
• Patients must have a life expectancy of at least 10 weeks.
• Patients must have ECOG performance status of 0-2.
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count of \>/= 500/uL, absolute lymphocyte count \>/= 200/uL, hemoglobin \>/= 8g/dL and platelet count \>/= 50,000/uL.
• Patients must not be infected at time of protocol entry, and should not be receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
• Patients must be HIV-negative.
• Patients must be willing to practice appropriate birth control methods during the study and for 3 months after the study is concluded.
• Patients must not be suffering from an autoimmune disease (including active graft-versus-host disease-GvHD, refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA) and should not be receiving immunosuppressive drugs.
• Patients must have adequate liver function (total bilirubin \</= 1.5mg/dl, SGOT \</= 2 times normal, normal prothrombin time).
• Patients must have adequate renal function (creatinine \< 3 times normal for age or creatinine clearance \> 80mg/min/1.73m2).
• Patients must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side-effects. Patients will be given a copy of the consent form.
• Patient must not have received treatment with other investigational agents within the last 4 weeks.

You may not qualify if:

• Richter's transformation (aggressive non-Hodgkin's lymphoma)
• active infection
• significant autoimmune disease (including active GvHD, ITP and AIHA)
• requirement for immunosuppressive drugs
• inadequate liver and/or renal function
• pregnancy or lactation
• refusal to practice birth control methods
• seropositive for HIV
• life expectancy less than 10 weeks

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

The Methodist Hospital

Houston, Texas, 77063, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Malcolm K Brenner, MD

  Center for Cell and Gene Therapy, Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director/Professor, Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: April 11, 2003
• First Posted: April 15, 2003
• Study Start: December 1, 2002
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: May 23, 2012

Record last verified: 2012-05

Locations

US (1)