Clinical Trial: Pilot Study of Radiation-Enhanced Allogeneic Cell Therapy for Progressive Hematologic Malignancy After Allogeneic Hematopoietic Stem Cell Transplantation

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pilot Study of Radiation-Enhanced Allogeneic Cell Therapy for Progressive Hematologic Malignancy After Allogeneic Hematopoietic Stem Cell Transplantation

Brief Summary:

Background:

  • Allogeneic hematopoietic stem cell transplantation (allotransplant) has been used to treat many kinds of cancer that develop in cells from the blood or immune system. After allotransplant, donor cells take over production of the recipient s blood and immune cells, and donor immune cells can directly attack and control tumor. However, for cancers that do not respond to allotransplant, there are no proven cures.
  • A single treatment with radiation can improve the potency of immune-cell therapies. This is probably because the tumor tissue is damaged in a way that new tumor proteins are exposed, attracting immune cells to the tumor. By giving only a single dose of radiation, the immune cells that are attracted to the tumor are allowed to survive and function in their usual way, traveling throughout the body and educating other immune cells to recognize tumor, and to activate and expand in order to kill the tumor cells. Some research has shown that radiation may have a widespread effect on stimulating the immune system, educating immune cells to recognize and control tumors that have not been radiated.

Objectives:

- To determine whether a single treatment of radiation will help donor immune cells control cancer after allotransplant without causing excessive side effects.

Eligibility:

  • Recipients: Individuals 18 years of age and older who have blood cancers that have not responded to allotransplant.
  • Donors: Healthy individuals 18 years of age and older who were previous allotransplant donors for one of the study recipients.

Detailed Summary:

Background:

  • The prognosis for patients with cancer who have relapsed or progressive disease after allogeneic hematopoietic stem cell transplantation (allotransplant) is poor. Effective therapies for patients who fail withdrawal of immune suppression and administration of donor lymphocyte infusions (DLI) have not been identified.
  • Increasing the efficacy of allotransplant without increasing toxicity is a major goal of transplantation research. A major research effort within the Experimental Transplantation and Immunobiology Branch (ETIB) is to identify ways to build on the allogeneic platform to treat relapse after allotransplant.
  • We hypothesize that a single fraction of radiation to tumor prior to administration of donor lymphocytes will increase the potency of systemic graft-versus-tumor (GVT) effects without increasing graft-versus-host disease (GVHD).

Objectives:

- To determine the safety, in relation to GVHD and allograft function, and efficacy, in terms of systemic tumor response, of administering single-fraction, targeted radiotherapy with or without DLI to patients with persistent tumor after allotransplant.

Eligibility:

  • Adults with hematologic malignancies that progress or recur after allotransplant, successful donor T cell engraftment, and trial of withdrawal of immune suppression.
  • Disease that is amenable to radiation as well as additional measurable disease outside the radiation field.
  • Subjects with treatment-refractory acute or chronic GVHD will not be eligi
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: Response to Graft Versus Host Disease (GVHD) Treatment [ Time Frame: Up to 100 days ]

    The following criteria is used to determine response to GVHD treatment. Complete response (CR) is complete resolution of all clinical signs and symptoms of acute GVHD. Partial response (PR) is 50% reduction in skin rash, stool volume or frequency, and/or total bilirubin. Failure to maintain adequate performance status (Karnofsky Score >/= 70%). Non-responder (NR) <50% reduction in skin rash, stool volume or frequency, and/or total bilirubin. Failure to maintain adequate performance status (Karnofsky Score </= 70%). Progressive disease (PD) is further progression of signs and symptoms of acute GVHD, and/or decline in performance status after the initiation of therapy.


    Original Primary Outcome: Safety defined by the development or exacerbation of acute or chronic graft-versus-host disease (GVHD); feasibility with respect to identification of patients with radiation-accessible and evaluable hematologic malignancy; and efficacy.

    Current Secondary Outcome: Number of Participants With Adverse Events [ Time Frame: 36 months ]

    Here is the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module.


    Original Secondary Outcome: To characterize the quantitative and qualitative effects of single-fraction radiation on circulating allogeneic immune cell populations and blood levels of potential regulatory/inflammatory cytokines.

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

    Dates:
    Date Received: September 24, 2009
    Date Started: September 2009
    Date Completion:
    Last Updated: August 6, 2015
    Last Verified: August 2015