Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide

NCT01604031 | Terminated Phase 1 DMC

• 1 other identifier: H-30087 TAIL
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to determine the safety and effectiveness of using special cells that may make the subject's immune system fight their chronic lymphocytic leukemia (CLL) in combination with a drug called Lenalidomide. To do this, the investigators will put a special gene into cancer cells that have been taken from the subject. 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 subject's immune system kill cancer cells. Additionally, the investigators 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). Some of these cells will then be put back into the subject's body with the goal that they will act like a vaccine and stimulate the immune system to attack the CLL cells. The investigators have already conducted a study similar to this in other subjects with CLL. In those subjects the investigators 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. The investigators think that this may be due to a high level of cells called T regulatory cells. T regulatory cells are part of the immune system and prevent excessive reactions from other cells in the body. Studies have shown that reducing T regulatory cells allows the body to fight the cancer for a longer period of time. Recent studies have shown that using Lenalidomide helps the body reduce T regulatory cells. Using Lenalidomide along with the injections (shots) might help the body fight the cancer for a longer period of time. Lenalidomide is also called Revlimid. In this study the investigators want to see if they can make the change in the immune system last longer by giving Lenalidomide before and at the same time as the vaccine. The investigators hope that this might produce a better response directed at the CLL cells. Subjects will receive injections for about a year

Conditions

B-cell Chronic Lymphocytic Leukemia

Keywords

B-CLL; vaccine; Lenalidomide; CTL

Outcome Measures

Primary Outcomes (5)

• Adverse Events after Lenalidomide with B-CLL cell vaccine

  To assess the safety of administration of lenalidomide combined with prolonged administration of CD40L expressing and IL-2 secreting B-CLL cells (B-CLL vaccine).

  week 60

• Changes in SP tumor cell population from pre-vaccine to four weeks post-vaccination

  To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden and on the side population of tumor cells.

  week 4

• Changes in SP tumor cell population from pre-vaccine to eight weeks post vaccination

  To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden and the side population of tumor cells.

  week 8

• Number of patients with a tumor response post vaccination

  To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden.

  4 weeks

• Number of patients with a tumor response post vaccination

  To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden.

  8 weeks

Study Arms (1)

B-CLL vaccine

EXPERIMENTAL

Patients will receive doses of vaccine at 2 week intervals for 5 doses and at 4 week intervals for doses 6-16. The injection will be performed subcutaneously in the deltoid region of the upper arm.

Biological: B-CLL Vaccine; Drug: Lenalidomide

Interventions

B-CLL Vaccine BIOLOGICAL

Patients will receive a fixed dose (2X10\^7) of IL-2 secreting B-cells together with (2X10\^7) of hCD40L expressing B-cells. Patients will receive doses of vaccine at 2 week intervals for 5 doses. Barring adverse events, an additional 11 doses of vaccine will be given, at 4 weekly intervals beginning on week 12 for a total period of one year or 16 vaccinations in total.

B-CLL vaccine

Lenalidomide DRUG

Subjects will begin lenalidomide 5 mg orally daily on day zero and will continue daily dosing until week 60 (4 weeks after the final dose of vaccine).

Also known as: Revlimid

B-CLL vaccine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ELIGIBILITY FOR BLAST COLLECTION (procurement):
• Patients with B-CLL (not in Richter's transformation) with measurable disease.
• Procurement consent signed and faxed to Research Coordinator
• HIV negative (can be pending at this time)
• ELIGIBILITY FOR VACCINE AND LENALIDOMIDE ADMINISTRATION (protocol entry):
• Manipulated B-CLL cells available (at least 6 injections)
• Patients with B-CLL (not in Richter's transformation) with measurable disease
• Patients must have a life expectancy of at least 10 weeks.
• Patients must be less than 75 years old
• 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:
• Absolute neutrophil count (ANC) of greater than or equal to 500/microL
• Absolute lymphocyte count (ALC) greater than or equal 200/microL,
• Hemoglobin greater than or equal 8 g/dL
• Platelet count greater than or equal 50,000/microL.

You may not qualify if:

• Infected at time of protocol entry, or receiving antibiotics (other than prophylactic trimethoprim sulfamethoxazole).
• Pregnant or lactating
• Suffering from an autoimmune disease (including refractory immune thrombocytopenia-ITP or refractory autoimmune hemolytic anemia-AIHA)
• Receiving immunosuppressive drugs.
• Received systemic steroids within 30 days of study enrollment
• Autologous hematopoietic stem cell transplant or fludarabine chemotherapy within 6 months of study enrollment
• History of allogeneic stem cell transplant
• Patients with congestive heart failure or significant arrhythmia
• Known hypersensitivity to thalidomide or lenalidomide.

Sponsors & Collaborators

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

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Lenalidomide

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Martha Mims, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Malcolm Brenner, MB, PhD

  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: Associate Professor

Study Record Dates

• First Submitted: May 4, 2012
• First Posted: May 23, 2012
• Study Start: February 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: February 8, 2016

Record last verified: 2016-02

Locations

US (1)