Clinical Trial: Study of Pomalidomide Combined With Modified DA-EPOCH and Rituximab in KSHV-Associated Lymphomas

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: 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 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 d

    Detailed Summary:

    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
      Sponsor: National Cancer Institute (NCI)

      Current Primary Outcome: (Phase I) To determine the maximum tolerated dose and/or recommended phase II dose of pomalidomide in combination with DA-EPOCH-R. [ Time Frame: one-year ]

      Original Primary Outcome: Same as current

      Current Secondary Outcome:

      • (Phase II) Evaluate overall survival in treatment naive patients with primary effusion lymphoma treated with pomalidomide in combination with modified DA-EPOCH-RP [ Time Frame: one-year ]
      • Evaluate response rates and progression free survival [ Time Frame: one-year ]


      Original Secondary Outcome: Same as current

      Information By: National Institutes of Health Clinical Center (CC)

      Dates:
      Date Received: August 27, 2014
      Date Started: August 15, 2014
      Date Completion:
      Last Updated: May 12, 2017
      Last Verified: May 5, 2015