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

Stopped early · Phase 2

Conditions studied: Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemias, Multiple Myeloma With Plasmacytoma

In brief

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. Design: * Donors will provide additional blood immune cells, called lymphocytes, through apheresis. Apheresis involves drawing blood, separating out the lymphocytes, and returning the rest of the blood to the donor. * Recipients will receive a single dose of radiation to the greatest amount of tumor that can be irradiated safely. Researchers will intentionally leave some tumor that will not be radiated in order to evaluate whether there is a widespread response to the treatment. * There are two treatment arms on the study. * Arm 1: Study participants who have donor lymphocytes available and who have not had major complications from the allotransplant will be given a dose of donor cells after they receive radiation, to provide an additional boost to the donor immune response. * Arm 2: Study participants who cannot receive donor lymphocytes because their donor is not available, they received an allotransplant from a partially matched relative, or they have had significant complications from the allotransplant - will receive radiation without additional donor lymphocytes. * All recipients will be followed closely for side effects and for tumor response to radiation with or without donor lymphocytes. Additional tests will be performed, including tumor biopsies, bone marrow samples, and blood draws, in order to study the immune effects of radiation and donor lymphocytes. * A separate, control group of allotransplant recipients will not receive radiation. This group will include participants whose transplant doctors plan to use donor lymphocyte therapy alone to control cancer progression. This group will donate blood immune cells through blood draws and apheresis. These cells will be examined to study the immune effects of receiving donor lymphocytes without radiation.

Key facts

Study ID

NCT00984165

Run by

National Cancer Institute (NCI)

People needed

18

Starts

2010-01-19

Expected to finish

2013-01-31

Last updated by the study team

2018-05-02

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• Treatment Subjects:
• Tumor-directed therapy within two weeks of DLI.
• Patients with rapid disease progression or aggressive tumor histology which, in the opinion of the principal investigator (PI), is likely to require urgent therapy within 60 days in order to preserve organ function or quality of life, and there is an available standard therapy to which the patient has a reasonable chance of responding.
• Progressive disease that, in the opinion of the PI, requires urgent standard therapy, e.g., threatened organ function, acceptable quality of life, etc.
• Uncontrolled GVHD, i.e., either acute GVHD Grade III or chronic-moderate/severe GVHD that has not responded to the current dose of systemic therapy or any history of steroid-refractory acute GVHD, Grade IV acute GVHD, or chronic-severe GVHD.
• Active infection that is not responding to antimicrobial therapy.
• Active psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by Principal Investigator and/or her designee).
• Pregnant or lactating. Subjects of childbearing potential must use an effective method of contraception. The effects of the immunosuppressive medications that could be required to treat GHVD are likely to be harmful to a fetus. The effects upon breast milk are also unknown and may be harmful to an infant.
• Absolute neutrophil count of less than 500 cells/microL. At the PIs discretion, patients with marrow replacement by tumor as the probable etiology of an absolute neutrophil count of less than 500 cells/microL may be eligible for enrollment.
• In order to prevent delay of potentially stabilizing palliative therapy, the following conditions will exclude eligibility: untreated active leptomeningeal involvement with malignancy, untreated brain metastasis, and other organ-threatening diseases in which palliative treatment options with reasonable probability of efficacy (15% or higher) are available. Patients with these conditions for whom available palliative options have been tried or deemed unacceptable but who otherwise meet eligibility criteria may, at the discretion of the PI, be considered for enrollment.
• Donor Subjects:
• History of a psychiatric disorder that the PI determines might compromise compliance with transplant protocol, or that does not allow for appropriate informed consent.
• Hypertension that is not controlled by medication, history of stroke, or severe heart disease (donors with symptomatic angina will be excluded). Donors with a history of coronary artery bypass grafting or angioplasty who are symptom free will receive a cardiology evaluation and be considered on a case-by-case basis.
• History of prior malignancy. However, cancer survivors who have undergone potentially curative therapy and have had no evidence of that disease for at least 5 years may be considered for lymphocyte donation on a case-by-case basis.
• Anemia (hemoglobin (Hb) less than 11 gm/dl) or thrombocytopenia (platelets less than 100,000 per ml). However, potential donors with Hb levels less than 11 gm/dl that is due to iron deficiency will be eligible as long as the donor is initiated on iron replacement therapy and the case is individually approved by NIH Department of Transfusion Medicine (DTM).
• Pregnancy. Donor Subjects of childbearing potential must use an effective method of contraception until after completion of apheresis. The effects of apheresis are unknown to be safe to a fetus.
• DLI Control Subjects:
• Tumor-directed therapy within two weeks of DLI.
• Uncontrolled GVHD
• Pregnant or lactating. Subjects of childbearing potential must use an effective method of contraception until after completion of apheresis. The effects of apheresis are unknown to be safe to a fetus.
• History of a psychiatric disorder that the PI determines might compromise compliance with protocol, or that does not allow for appropriate informed consent.
• Hypertension that is not controlled by medication, history of stroke, or severe heart disease (subjects with symptomatic angina will be excluded).

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.