Donor Lymphocyte Infusion in Treating Patients With Recurrent or Persistent Hematologic Cancer After Donor Stem Cell Transplant

Study Overview
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Brief Summary
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RATIONALE: Giving an infusion of donor lymphocytes may be able to kill cancer cells in patients with hematologic cancer that has come back after a donor stem cell transplant. PURPOSE: This clinical trial is studying how well donor lymphocyte infusion works in treating patients with recurrent or persistent hematologic cancer after donor stem cell transplant.

Detailed Description
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OBJECTIVES: Primary Determine if the complete response rate exceeds 10% in patients with recurrent or persistent hematologic malignancies treated with donor lymphocyte infusion. Secondary Estimate the complete response rate in these patients. Assess the toxicity of donor lymphocyte infusion in these patients. OUTLINE: Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease.

Official Title
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Cellular Infusions in Patients With Recurrent or Persistent Hematologic Malignancies After Allogeneic Stem Cell Transplant

Conditions
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Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: donor lymphocytes


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Has undergone allogeneic stem cell transplantation (ASCT) for hematologic malignancy at least 30 days ago No failure to engraft following transplant No active acute or chronic graft-versus-host disease (GVHD) Minimal GVHD allowed Persistent or relapsed disease after ASCT, including 1 of the following: Chronic myelogenous leukemia (CML), meeting any of the following criteria: Molecular relapse (may be treated with imatinib mesylate after transplant), as defined by any of the following: ASCT was non-T-cell depleted, a negative bcr/abl was documented by PCR post-transplant, and bcr/abl is now detectable by 2 consecutive PCR determinations > 30 days apart ASCT was non-T-cell depleted and bcr/abl is detectable by PCR at any time after day 180 post-transplant Cytogenetic relapse after 3-6 months of imatinib mesylate Relapsed chronic phase, accelerated phase, or blastic phase CML after 3-6 months of imatinib mesylate Must currently be in chronic phase or accelerated phase CML only Patients with blastic phase CML must attain a second chronic phase Acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes, meeting any of the following criteria: Molecular relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific molecular abnormality detectable by PCR Cytogenetic relapse, as evidenced by < 5% blasts in the bone marrow and the patient's leukemia-specific chromosome abnormality detectable by standard cytogenetics at any time after day 60 post-transplant Hematologic relapse, as evidenced by > 20% blasts in bone marrow or soft tissue recurrence Must be treated with chemotherapy after transplant, but before study donor lymphocyte infusion (DLI) Multiple myeloma Relapsed disease or recurrence of M-protein after thalidomide or other salvage treatment Prior post-transplant documentation of disappearance of M-protein by immunofixation Residual or progressive disease Rising M-protein level at any time post-transplant (measured at 3-month intervals) Original M-protein detectable at 6 months post-transplant Immune protein electrophoresis (IPEP) is required to show that M-component is the same on day 60 post-transplant as pre-transplant Residual (> 5%) plasma cells in bone marrow Relapsed non-Hodgkin lymphoma or Hodgkin lymphoma Relapse or progression of disease must be evidenced within 3 months prior to donor lymphocyte infusion by physical exam, radiographic studies, or molecular studies Tumor should be re-biopsied to determine histology If Epstein-Barr virus (EBV) lymphoma is suspected, peripheral blood must be assayed for EBV genome (i.e., EBV DNA testing by PCR) within the past 30 days EBV infection with associated pancytopenia Persistent or refractory pancytopenia with EBV genome detected by PCR in the peripheral blood Refractory pancytopenia is defined as pancytopenia that is poorly responsive to growth factors and/or transfusions EBV lymphoproliferative disorder Clonal lymphadenopathy that is refractory to standard therapy with acyclovir and immunoglobulin (DLI may be given with rituximab) Not a candidate for repeat ASCT Chimerism status is not required for determining eligibility for DLI Patients eligible for allogeneic ASCT, but for whom DLI is offered as the first option, should have full donor chimerism at relapse or after therapy for relapsed disease Patients with relapsed underlying disease after transplant who achieved remission after chemotherapy are allowed No CNS recurrence that is not cleared by standard chemotherapy CNS remission status must be maintained for 2 weeks Original hematopoietic progenitor stem cell donor must be available for cell donation No syngeneic donors PATIENT CHARACTERISTICS: Karnofsky performance status 60-100% Life expectancy ≥ 8 weeks Creatinine < 3 mg/dL ABO/Rh and CMV IgG/IgM status known No HIV1 and HIV2 antibody Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months (males) or 6 months (females) after completion of study treatment PRIOR CONCURRENT THERAPY: See Disease Characteristics

Ages Eligible for Study
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Maximum Age: 76 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusion<br>Patients receive up to four donor lymphocyte infusions at least 1 month apart in the absence of disease progression, unacceptable toxicity, or uncontrolled graft-versus-host disease | Biological: donor lymphocytes<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate | continued or induced complete remission after DLI | 100 days post DLI | 
| Duration of Complete Response in Months (Maximum 12) | For participants who achieve a complete remission after DLI, the duration of time until 1) relapse or 2) death in remission or 3) subsequent DLI or 4) last followup (at 1 year after DLI) | 1 year post DLI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Graft-versus-host Disease | development of grade III-IV acute graft-versus-host disease (GVHD) per Glucksberg criteria | 100 days post DLI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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accelerated phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, childhood chronic myelogenous leukemia, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent adult grade III lymphomatoid granulomatosis, Waldenstrom macroglobulinemia, recurrent childhood grade III lymphomatoid granulomatosis, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent childhood small noncleaved cell lymphoma, de novo myelodysplastic syndromes, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent mycosis fungoides/Sezary syndrome, cutaneous B-cell non-Hodgkin lymphoma