Induction of Anti-Myeloma Stem Cell Immunity With Infusions of Autologous Activated T Cells Armed With OKT3 x Rituxan (Anti-CD3 x Anti-CD20) Bispecific Antibody (CD20Bi) (Phase I).
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Cell-based toxicities according to NCI CTCAE v3.0 criteria
研究概览
简要总结
RATIONALE: Giving chemotherapy followed by treated T cells before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or by killing them. After treatment, stem cells are collected from the patient's blood and stored. High-dose chemotherapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
PURPOSE: This phase I trial is studying the side effects and best way to give treated T cells followed by stem cell transplant in treating patients with multiple myeloma.
详细描述
OBJECTIVES:
Primary
- To test the feasibility and safety of infusing anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells (CD20Bi-AATC) before stem cell mobilization and collection for autologous peripheral blood stem cell transplantation (PBSCT) in patients with multiple myeloma.
Secondary
- To explore functional changes in immune cell populations as a consequence of immunotherapy to test the hypothesis that CD20Bi-AATC can induce anti-clonogenic myeloma precursor cell (CMPC) effect as measured by cytotoxicity; serum cytokine levels; and serum antibody titers to myeloma cells pre-immunotherapy, after immunotherapy, and after high-dose chemotherapy and autologous PBSCT.
- To explore whether the infusion of CD20Bi-AATC reduces the proportion of plasma cells with the CD20+ CMPC phenotype in patients' bone marrow as assessed by multi-color flow cytometry before and after immunotherapy.
- To assess the proportion of bone marrow colony-forming assays before induction or salvage chemotherapy, pre-immunotherapy, and post-immunotherapy to determine whether the infusion grossly affects the bone marrow progenitor populations.
- To explore whether infusions of CD20Bi-AATC induce a B-cell defect causing an immunoglobulin deficiency after autologous PBSCT.
- To measure immunoglobulin deficiency after autologous PBSCT (e.g., quantitative IgG, IgM, and IgA levels and number of circulating T- and B-cell subsets).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of multiple myeloma
- •Candidate for high-dose chemotherapy and autologous stem cell transplantation
- •No definite morphologic evidence of myelodysplasia on pretreatment bone marrow
- •PATIENT CHARACTERISTICS:
- •ECOG performance status (PS) 0-2 or Karnofsky PS 70-100%
- •ANC > 500/mm^3
- •Platelet count ≥ 75,000/mm^3
- •Total bilirubin ≤ 2.0 mg/dL
- •AST and ALT ≤ 3 times upper limit of normal
- •Creatinine ≤ 2.0 mg/dL
- •LVEF ≥ 45%
- •Corrected pulmonary diffusion capacity ≥ 50%
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No uncontrolled infections or other severe medical problems such as adrenal dysfunction
- •No other active malignancy (except for nonmelanoma skin cancer) that requires myelosuppressive chemotherapy or radiotherapy
- •No HIV infection
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •On-chemotherapy induction with thalidomide or lenalidomide with dexamethasone is allowed
- •No prior stem cell transplantation
- •No more than 2 prior treatment regimens (including the one during which patients undergo leukapheresis for T-cells)
- •No more than 4 courses of lenalidomide in combination with other agents or as a single agent over a 1-year period
- •No other concurrent immunotherapy, radiotherapy, chemotherapy, or anti-myeloma therapy at the time of the anti-CD3 x anti-CD20-armed ATC infusion
排除标准
- 未提供
研究组 & 干预措施
Armed-activated T cells/Immunotherapy
At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis for G-CSF-mobilized autologous T-cells.
干预措施: anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells (Biological)
Armed-activated T cells/Immunotherapy
At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis for G-CSF-mobilized autologous T-cells.
干预措施: autologous hematopoietic stem cell transplantation (Procedure)
Armed-activated T cells/Immunotherapy
At least 1-3 weeks after the second infusion, patients receive high-dose chemotherapy and then undergo autologous peripheral blood stem cell transplantation. Patients then undergo leukapheresis for G-CSF-mobilized autologous T-cells.
干预措施: peripheral blood stem cell transplantation (Procedure)
结局指标
主要结局
Cell-based toxicities according to NCI CTCAE v3.0 criteria
时间窗: Up to week 4 after chemotherapy
Ability to mobilize the number of stem cells required for autologous peripheral blood stem cell transplantation (PBSCT)
时间窗: By day 30 after autologous stem cell transplant (ASCT)
次要结局
- Functional changes in immune cell populations(Prior to immunotherapy (IT), after IT, high dose chemotherapy (HDC)/ autologous stem cell transplant (ASCT) and boost infusion)
- Engraftment of neutrophils(At day 28 after autologous PBSCT)
- Assess proportion of erythroid blast-forming unit (BFU)-E, colony forming unit-granulocyte-macrophage (CFU)-GM, CFU-GEMM (granulocyte, erythrocyte, monocyte, megakaryocyte) & erythroid colony forming (CFU-E)(Prior to induction or salvage chemotherapy; Pre & post IT)
研究者
Jeffrey Zonder
Principal Investigator
Barbara Ann Karmanos Cancer Institute