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Investigator(s):
Nancy M. Hardy, M.D. Principal Investigator Phone: 301-451-1406 hardyn@mail.nih.gov	Deborah E. Citrin, M.D. Lead Associate Investigator Phone: 301-496-5457 citrind@mail.nih.gov
Referral Contact(s):
Zetta Blacklock, R.N., B.S., B.S.N. Transplant Coordinator Phone: 301-594-2056 Fax: 301-451-5578 bblacklock@mail.nih.gov	Sheila Phang, R.N., M.S. Transplant Coordinator Phone: 301-435-9379 Fax: 301-451-5578 sphang@mail.nih.gov

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Key Eligibility Criteria:

Treatment Subjects:

• Must have received allotransplant for hematologic malignancies and have disease progression
• ≥ 2 distinct sites of disease
• ≥ 1 site must be solid-phase and amenable to radiation
• Must have disease discrete from local effects of radiation that can be evaluated for systemic response to therapy
• Persistent disease ≥ 4 weeks after both of the following events occur:
• Donor T-cell engraftment (> 90% of peripheral blood lymphocyte (PBL) T cells)
• Trial of withdrawal of immunosuppression, including trials discontinued due to GVHD
• 18–75 years of age
• ECOG 0–3 (Karnofsky ≥ 50%)
• Not pregnant or nursing
• No tumor-directed therapy within 2 weeks of radiation
• No uncontrolled acute GVHD Grade III, chronic-moderate/severe GVHD, history of steroid-refractory or Grade IV acute GVHD, or chronic-severe GVHD
• No untreated active leptomeningeal malignancy, brain metastasis, or other organ-threatening disease that have available palliative treatment options with reasonable efficacy (15%)
• No active infection not responding to antimicrobial therapy
• Neutrophils ≥ 500/microL, unless marrow tumor is probable etiology
• No rapid disease progression likely to require urgent therapy within 60 days, with conventional therapy option with reasonable efficacy
• Arm A
• Patients with minimal history of GVHD grade 0–I acute GVHD or mild-chronic GVHD off systemic immunosuppressive therapy
• Available source of donor lymphocyte cell product
• Donors are first-degree relatives with genotypic identity at 5-6/6 HLA loci (HLA-A, -B, and -DR) or matched, unrelated donors from whom lymphocyte cell products are available for use on this trial
• Arm B
• Patients with any history of Grade III acute GVHD or moderate/severe chronic GVHD
• Patients with controlled acute GVHD (Grade I–III) or chronic-moderate/severe GVHD on stable (4 weeks) or tapering dose of systemic immunosuppression and/or topical therapy (GVHD prophylaxis with steroid-sparing agents is permitted with the exception of sirolimus; sirolimus must be switched to another agent 2 weeks prior to enrollment)
• Patients with no donor lymphocytes available
• Patients whose allotransplant was from a haploidentical (< 5/6 genotypic identity) related donor

Donor Subjects:

• 18–90 years of age
• Previous allotransplant donor for one of the study recipients
• No uncontrolled hypertension, history of stroke, or severe heart disease
• No prior malignancy (donors who have received potentially curative therapy with no evidence of disease after 5 years may be eligible)
• Hb ≥ 11 g/dL and platelets ≥ 100,000/mL (except iron deficiency anemia)
• Not pregnant or nursing
• Adequate venous access for apheresis
• HIV negative, hepatitis B surface antigen negative, and hepatitis C antibody negative

DLI Control Subjects (Arm A):

• Patients with persistent tumor after allotransplant for whom a DLI is planned and available
• 18–75 years of age
• ECOG 0–3 (Karnofsky ≥ 50%)
• Patients with Grade 0–I acute GVHD or mild-chronic GVHD off systemic immunosuppressive therapy (e.g., steroids)
• Donors are first-degree relatives with genotypic identity at 5-6/6 HLA loci (HLA-A, -B, and -DR) or matched, unrelated donors from whom lymphocyte cell products are available for use on this trial
• Persistent disease ≥ 4 weeks after both of the following events occur:
• Donor T-cell engraftment (> 90% of PBL T cells)
• Trial of withdrawal of immunosuppression, including trials discontinued due to GVHD
• No tumor-directed therapy within 2 weeks of DLI

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Study Outline:

• Donor participants will provide lymphocytes through apheresis
• Treatment participants will receive an 8-Gy dose of radiation delivered in a single fraction to as much tumor as safely possible; some tumor will not be radiated in order to evaluate whether there will be a widespread response to the treatment
• There are two treatment arms on the study:
• Arm A:
• Treatment participants who have donor lymphocytes available and who have not had severe or uncontrolled GVHD will be given a donor lymphocyte infusion one day after they receive radiation to provide an additional boost to the donor immune system
• Arm B:
• Treatment participants who cannot receive donor lymphocytes (e.g., their donor is not available, they received an allotransplant from a partially matched relative, they have had severe GVHD, or they are being treated for active GVHD) will receive radiation without additional donor lymphocytes
• All treatment participants will be followed closely for side effects and for tumor response to radiation with or without donor lymphocytes
• Additional tests will be performed, including an additional PET-CT scan, tumor biopsies, bone marrow samples, and blood draws, in order to study the systemic effects of radiation on the tumor and the donor immune system
• There will be a control group on this study, which will include allotransplant recipients whose transplant doctors recommend donor lymphocyte therapy alone to treat cancer progression
• This group will not receive radiation; the planned DLI will be administered on this trial
• This group will donate blood immune cells before and after DLI through blood draws and apheresis; these cells will be compared to cells from Arm A participants to study the immune effects of DLI alone

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Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• FAQs about this study - provides information for patients about the trial such as frequency and duration of visits, costs, how to enroll, and study outline.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 9/20/12
Updated: 12/2/11