Treatment of B-CLL With Human IL-2 and CD40 Ligand and Plasmid Gene Modified Autologous Tumor Cells

NCT00078520 | Completed Phase 1 DMC

• 2 other identifiers: H11967CLIPA
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for patients that have chronic lymphocytic leukemia (CLL). This research study aims 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 patients body. 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 experiments in animal and human cells in vitro demonstrated can help IL-2 perform better. Some of these cells will then be put back into the patient's body. 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. An experimental treatment similar to this has already been used in children and similar experimental treatments are being used in adults with other cancers.

Conditions

Leukemia; Leukemia, B-Cell, Chronic

Keywords

Leukemia

Outcome Measures

Primary Outcomes (1)

• safety of injections of autologous malignant B cells from B-CLL patients, which have been modified to secrete hIL-2 and hCD40L.

  12 weeks

Secondary Outcomes (2)

• anti-tumor immune responses

  15 years

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

  15 years

Study Arms (3)

Dose Level 1

EXPERIMENTAL

Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level.

Biological: Dose Level 1

Dose Level 2

EXPERIMENTAL

Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level.

Biological: Dose Level 2

Dose Level- Fixed Dose

EXPERIMENTAL

Patients may be treated with a minimum of 3-6 injections of their IL-2-secreting and CD40L-expressing autologous B-CLL cells, separated by one to two weeks in an immunological treatment window. 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 while an escalating number of CD40L-expressing B-CLL cells will be given at each dose-level.

Biological: Dose Level 2- Fixed Dose

Interventions

Dose Level 1 BIOLOGICAL

IL-2-B-CLL 2 x 10\^7; CD40L-B-CLL 0

Dose Level 1

Dose Level 2 BIOLOGICAL

IL-2-B-CLL 2 x 10\^7; CD40L-B-CLL 2 x 10\^6

Dose Level 2

Dose Level 2- Fixed Dose BIOLOGICAL

IL-2-B-CLL 2 x 10\^7; CD40L-B-CLL 2 x 10\^7

Dose Level- Fixed Dose

Eligibility Criteria

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

You may qualify if:

• Patients must have a life expectancy of at least 10 weeks.
• Patients must have ECOG performance status of 0-2 as below: 0 = up and about, no restriction, 1 = Ambulatory, no strenuous activity, 2 = Ambulatory, capable of self-care appropriate for age. Up and about \> 50% of time, but unable to carry out any physical activities or attend school, 3 = Limited self-care only. Up and about \< 50% of time, 4 = Disabled, no self care. Bedridden or confined to chair.
• Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and must have an absolute neutrophil count (ANC) of \> / = 500/mL, absolute lymphocyte count (ALC) \> / = 200/mL, hemoglobin \> / = 8g/dL, and platelet count \> / = 50,000/mL
• 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. This includes total abstinence, oral contraceptives, an intrauterine device, contraceptive implants under the skin, contraceptive injections (Depo-Provera). Contraceptive foam with a condom is allowed. The male partner should use a condom.
• 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 less than 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:

• Richters transformation (aggressive non-Hodgkins 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, 77030, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; 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

  Baylor College of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dist Serv Prof, Center for Gene Therapy

Study Record Dates

• First Submitted: March 1, 2004
• First Posted: March 2, 2004
• Study Start: January 1, 2003
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: January 21, 2020

Record last verified: 2020-01

Locations

US (1)