Treatment of B-Chronic Lymphocytic Leukemia (B-CLL) With Autologous CD40 Ligand and IL-2-Expressing Tumor Cells

NCT00458679 | Completed Phase 1 DMC

• 2 other identifiers: 19747-PRIMALPRIMAL
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

We would like patients to be in a research study to determine the safety and effectiveness of special cells that may make their own immune system fight their 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 their immune system kill cancer cells. Additionally, we will stimulate the cancer cells with normal embryonic fibroblasts (cells that develop into normal connective tissues in the body) so that they will make another natural protein called CD40 ligand (CD40L). Studies of cancers in animals suggest IL-2 performs better when mixed with CD40L. Some of these cells will then be put back into the patients body with the goal that they will act like a vaccine and stimulate their immune system to attack the CLL cells. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that combining substances like IL-2 and CD40L with cancer cells help the body recognize and kill cancer cells. We have already conducted a study similar to this in patients with CLL. In that study, the subjects received about three months of injections (shots). In those subjects we saw some changes in the subject's immune system that might indicate that the modified cells were helping their immune system fight the cancer. However, in most of the subjects this change in the immune system went away after the injections were stopped. In this study we want to see if we can make the change in the immune system last longer by giving more injections over a longer period of time. We hope that this might produce a better response directed at the CLL cells. We will also be looking at the effect on cells called cancer stem cells which grow into the CLL cells we see in the blood. Specifically, this study will allow subjects to receive the injections for up to one year.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Keywords

CHRONIC LYMPHOCYTIC LEUKEMIA (B-CLL); CD40 LIGAND AND IL-2-EXPRESSING TUMOR CELLS

Outcome Measures

Primary Outcomes (1)

• To measure adverse events of patients receiving prolonged immunization with an autologous B-CLL vaccine expressing CD40L and IL2

  10 weeks

Secondary Outcomes (1)

• Measurement of MHC-restricted or unrestricted anti-tumor immune responses

  2 years

Study Arms (1)

Vaccine

EXPERIMENTAL

autologous B-CLL vaccine expressing CD40L and IL2

Biological: CD40 LIGAND AND IL-2-EXPRESSING TUMOR CELLS VACCINE

Interventions

CD40 LIGAND AND IL-2-EXPRESSING TUMOR CELLS VACCINE BIOLOGICAL

Patients will receive a fixed dose (2 x 10\^7) of IL-2 secreting B-cells together with (2 x 10\^7)hCD40L expressing B-cells. They will receive 18 deltoid injections over 52 weeks.

Vaccine

Eligibility Criteria

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

You may qualify if:

• Eligibility for blast collection:
• Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richter's transformation) with measurable disease.
• Procurement consent signed and faxed to Research Coordinator
• Eligibility for Vaccine Administration (protocol entry)
• Manipulated B-CLL cells available (at least 12 injections)
• Patients are eligible for administration of their vaccine if they present with B-CLL (not in Richter's transformation) with measurable disease
• Patients must have a life expectancy of at least 10 weeks.
• Patients must have ECOG performance status of 0-2 as below:
• Grade 0: Up and about, no restriction
• Grade 1: Ambulatory, no strenuous activity
• Grade 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.
• Grade 3: Limited self-care only. Up and about \< 50% of time
• Grade 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 greater than or equal to 500/uL, absolute lymphocyte count (ALC) greater than or equal to 200/uL, hemoglobin greater than or equal to 8 g/dL and platelet count greater than or equal to 50,000/uL.
• 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 \[Registered\]). Contraceptive foam with a condom is allowed. The male partner should use a condom.

You may not qualify if:

• Infected at time of protocol entry, or receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
• HIV positive
• Pregnant or lactating
• Suffering from an autoimmune disease (including active graft-versus-host disease-GvHD, refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA)
• Receiving immunosuppressive drugs
• Patients without adequate cardiac function (congestive heart failure, significant arrhythmia)

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, Lymphocytic, Chronic, B-Cell

Interventions

CD40 Ligand

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

Intervention Hierarchy (Ancestors)

Membrane Glycoproteins; Glycoproteins; Glycoconjugates; Carbohydrates; Tumor Necrosis Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Membrane Proteins; Biological Factors

Study Officials

• Malcolm K Brenner, MB, PhD

  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: Professor/Director Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: April 9, 2007
• First Posted: April 11, 2007
• Study Start: December 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: August 1, 2013
• Last Updated: February 3, 2014

Record last verified: 2014-01

Locations

US (1)