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

This study is currently recruiting participants.
Verified January 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Houston Methodist Hospital
Information provided by (Responsible Party):
Martha Mims, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01604031
First received: May 4, 2012
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Biological: B-CLL Vaccine
Drug: Lenalidomide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Adverse Events after Lenalidomide with B-CLL cell vaccine [ Time Frame: week 60 ] [ Designated as safety issue: Yes ]
    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).

  • Changes in SP tumor cell population from pre-vaccine to four weeks post vaccination [ Time Frame: week 4 ] [ Designated as safety issue: No ]
    To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden.

  • Changes in SP tumor cell population from pre-vaccine to eight weeks post vaccination [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden.


Estimated Enrollment: 15
Study Start Date: February 2013
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B-CLL vaccine
Patients will receive doses of vaccine at 2 week intervals for 5 doses. The injection will be performed subcutaneously in the deltoid region of the upper arm.
Biological: B-CLL Vaccine
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.
Drug: Lenalidomide
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).
Other Name: Revlimid

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.
  • Patients must be willing to practice appropriate birth control methods during the study and for 28 days after their participation in the treatment portion of the study is concluded. Females of childbearing potential (FCBP) (see Note below) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. In the full protocol see Appendix G: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix: Education and Counseling Guidance Document.
  • Patients must have adequate liver function:
  • Total bilirubin less than or equal to 1.5 mg/dl, SGOT less than or equal to 3 times normal
  • Normal prothrombin time
  • Patients must have adequate renal function (creatinine clearance greater than 50 mg/ml).
  • Patients provide informed consent.
  • Patient must not have received treatment with other investigational agents within the last 4 weeks.
  • All study participants (treatment) must be registered in the RevAssist Program and be willing to comply with the requirements of RevAssist.

Note: A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Exclusion Criteria:

EXCLUSION CRITERIA FOR VACCINE ADMINISTRATION (protocol entry):

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01604031

Contacts
Contact: Martha Mims, MD 713-798-7535 mmims@bcm.edu
Contact: Stacy Campos 713-441-6279 sdmay@houstonmethodist.org

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Martha Mims, MD    713-798-7535    mmims@bcm.edu   
Contact: Stacy Campos    713-441-6279    sdmay@houstonmethodist.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Houston Methodist Hospital
Investigators
Principal Investigator: Martha Mims, MD Baylor College of Medicine
Principal Investigator: Malcolm Brenner, MB, PhD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Martha Mims, Associate Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01604031     History of Changes
Other Study ID Numbers: H-30087 TAIL
Study First Received: May 4, 2012
Last Updated: January 20, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
B-CLL
vaccine
Lenalidomide
CTL

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014