Phase I/II Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas (Primary Effusion Lymphoma and Large Cell Lymphoma Arising in KSHV-Associated Multicentric Castleman Disease)

National Cancer Institute (NCI)0 个研究点开始时间: 2014年8月15日最近更新: 2018年8月31日

适应症

干预措施

试验速览

阶段: 1 期
状态: 撤回
发起方: National Cancer Institute (NCI)
主要终点: (Phase I) To determine the maximum tolerated dose and/or recommended phase II dose of pomalidomide in combination with DA-EPOCH-R.

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

Background:

The chemotherapy combination DA-EPOCH-RP includes the drugs etoposide (E), prednisone (P), vincristine (O), cyclophosphamide (C), doxorubicin (H), rituximab (R), and pomalidomide (P). Researchers want to see if including pomalidomide will help people with two rare lymphomas.

Objectives:

To study the safety and efficacy of the chemotherapy drugs DA-EPOCH-RP.

Eligibility:

Adults at least 18 years old. They must have primary effusion lymphoma or large cell lymphoma arising from Kaposi sarcoma Herpesvirus-associated multicentric Castleman disease.

Design:

Participants will be with screened with blood tests, scans, spinal tap, and bone marrow sample. They may have skin or lymph node samples taken and fluid removed from around some organs.
Participants will have breathing and eye tests. A camera may take pictures inside their body.
Participants will take pomalidomide alone by mouth for up to 21 days. Then they will get rituximab by intravenous (IV) catheter, which is a small tube that goes into a vein..
Participants will have an IV inserted in an arm or chest vein to get the IV chemotherapy drugs, at the same time the will take pomalidomide by mouth for 5 days.
They will get DA-EPOCH-RP in 21-day cycles. Most people will have 6 cycles.
They will get 4 study drugs by IV for 5 days and 2 others by mouth for 5 days.
They will get daily filgrastim injections in the skin until white blood counts are acceptable
For 2 days of some cycles, methotrexate will be injected into the spinal fluid.
After completing EPOCH-RP, some participants who have Kaposi sarcoma will be prescribed pomalidomide for 3-weeks, followed by a one week break, for up to 12 months.
Participants will repeat the blood tests often. They will also have repeated medical history, physical exam, urine and stool tests, and pictures of any rashes associated with these lymphomas.
Participants will have several follow-up visits over 4 years.

详细描述

Background:

Kaposi sarcoma herpesvirus (KSHV)-associated primary effusion lymphoma (PEL) and large cell lymphoma arising from KSHV-MCD are aggressive B cell neoplasms with clinicopathologic and molecular profiles distinct from other AIDS-related lymphomas.
There are no prospective studies on these rare lymphomas. Clinical experience is limited; however, reported prognosis is poor, with median survival estimated at less than 6 months using conventional CHOP-like chemotherapy.
Novel treatment is urgently needed for KSHV-associated lymphomas, and the therapeutic approach must take into account concurrent KSHV-associated malignancies which are commonly seen in this patient population
Pomalidomide, an immune-modulatory derivative (IMiD) of thalidomide has in vitro

direct antitumor effect in KSHV-lymphomas as well as immune modulatory and antiangiogenic effects that may be beneficial in treating both KSHV-NHL and in many patients, concurrent KS.

Rituximab, an anti-CD20 monoclonal antibody, has recently been shown to be an active agent in the management of KSHV-MCD. Although PEL is a CD20-negative tumor, advances in the understanding the biology of KSHV-infection of B-cells, the pathobiology of IL-6 syndromes in KSHV-MCD and KSHV-NHL, and clinical experience using rituximab in the treatment of KSHV-MCD support use of rituximab in the treatment of KSHV-NHL, especially in patients with concurrent KSHV-MCD.
Modified dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA)-EPOCH is an anthracycline-based regimen that allows for personalization of dose-intensity showing that inclusion of etoposide and infusional administration decreases tumor cell resistance.
The use of DA-EPOCH in combination with rituximab for the treatment of HIVassociated diffuse large B-cell lymphoma or Burkitt lymphoma has been shown to be safe and effective.
Given the central role of controlling HIV viremia with combination antiretroviral therapy (cART) in the management of KSHV-associated malignancies, as well as the likely contribution of uncontrolled HIV viremia to PEL pathogenesis, cART will be employed as an important part of the treatment regimen.

Objectives:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 99 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

未提供

排除标准

未提供