Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells + Lenalidomide
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Adverse Events after Lenalidomide with B-CLL cell vaccine
研究概览
简要总结
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
详细描述
Previously, some of the cancer cells were taken from the subject's body and separated in the laboratory and a specially produced human virus (adenovirus) that carries the IL-2 gene was put into the cells. Adenovirus is a common virus found in human respiratory systems. In its normal state, it can reproduce and cause a respiratory infection. Respiratory illnesses caused by adenovirus infections range from the common cold to pneumonia, croup and bronchitis. This adenovirus has been changed in the laboratory so that it is not likely to reproduce or cause an infection once it is in the body. The gene transfer method used in this study tries to add copies of the IL2 gene that increases the immune response against a tumor.
The rest of the cancer cells have been stimulated to express on their surface a substance called the human CD40L. These substances (IL-2 and CD40L), already naturally present in the body, are meant to help the immune system fight the cancer.
At the point that the doctor feels the subject should begin treatment on this protocol, the treatment will be as follows:
The subject will begin taking Allopurinol by mouth at 300 mg and will continue taking Allopurinol daily for 14 days. Allopurinol is also called Zyloprim and it will be taken to prevent tumor lysis syndrome. Tumor lysis syndrome can be a serious condition that occurs sometimes when cancer treatment is started. Tumor lysis syndrome can cause other medical problems.
Two days after Allopurinol was started, the subject will begin taking Lenalidomide. The Lenalidomide dose will be 5 mg taken by mouth daily. The subject should swallow the capsules whole with water at the same time each day and should not break, chew or open the capsules. Females of childbearing potential who are caring for the subject should not touch the lenalidomide capsules or bottles without gloves. If a dose of lenalidomide is missed, it should be taken as soon as possible on the same day. If it is missed for the entire day, it should not be made up. If more than the prescribed dose is taken of lenalidomide and the subject feels poorly, s/he should seek emergency medical care and tell the study staff right away. The subject will get 1 cycle of drug per month. A max of a 28-day supply of the drug will be provided at one time. If the subject has bad side effects the doctor may tell him/her not to take the lenalidomide for a short time period or may be removed from the study. Otherwise, the subject will continue daily dosing with Lenalidomide for approximately 1 year, until four weeks after the final vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
- •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 ml/min).
- •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 REMS® Program and be willing to comply with the requirements of REMS® .
- •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).
排除标准
- •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.
研究组 & 干预措施
B-CLL vaccine
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.
干预措施: B-CLL Vaccine (Biological)
B-CLL vaccine
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.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Adverse Events after Lenalidomide with B-CLL cell vaccine
时间窗: week 60
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
时间窗: week 4
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.
Changes in SP tumor cell population from pre-vaccine to eight weeks post vaccination
时间窗: week 8
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.
Number of patients with a tumor response post vaccination
时间窗: 8 weeks
To determine the effects of administration of lenalidomide combined with CD40L expressing and IL-2 secreting B-CLL cells on overall disease burden.
次要结局
未报告次要终点
研究者
Martha Mims
Associate Professor
Baylor College of Medicine