Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Pilot Study of Prophylactic Dose-Escalation Donor Lymphocyte Infusion After T Cell Depleted Allogeneic Stem Cell Transplant in High Risk Patients With Hematologic Malignancies
This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.
PRIMARY OBJECTIVES: I. To determine the feasibility of escalating dose regimen (EDR) donor lymphocyte infusion (DLI) as measured by the proportion of patients who receive at least one DLI. SECONDARY OBJECTIVES: I. To assess progression free survival (PFS) at 2 years after stem cell transplant (SCT) for high-risk hematologic malignancies receiving T-cell depleted grafts followed by escalating dose regimen (EDR) prophylactic DLI compared to historical controls not receiving DLI. II. To assess the safety of EDR DLI for high-risk hematologic malignancies as measured by cumulative incidence of severe grade III-IV acute graft-versus-host disease (GVHD). III. To measure outcomes of grade II-IV acute GVHD, non-relapse mortality, overall survival and chronic GVHD of EDR DLI. IV. To assess the full donor chimerism rate in the CD3 compartment and immune reconstitution after EDR DLI. OUTLINE: Patients receive DLI intravenously (IV). Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 2 years.
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
Progression Free Survival (PFS)
Accelerated Phase Chronic Myelogenous Leukemia
therapeutic allogeneic lymphocytes
Study Arms / Comparison Groups
Description: Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
April 4, 2013
Primary Completion Date
Inclusion Criteria: - INCLUSION CRITERIA PRIOR TO TRANSPLANT: - The clinical trial will be offered to all high risk (defined 3 below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors - Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning: - Refractory acute myelogenous or lymphoid leukemia - Relapsed acute myelogenous or lymphoid leukemia - Myelodysplastic syndromes with 5% or more blasts - Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase - Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant - High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen - DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors - T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen - Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant - Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS - Eligible for allogeneic transplant in the treating physicians' judgment and by institutional standards - ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT: - Donor lymphocytes available or able to be collected - No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude - Absolute neutrophil count >= 500/μl - Platelet count >= 20,000/μl without transfusion for 7 days - Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN) - Bilirubin =< 3 x ULN - No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI - No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded Exclusion Criteria: - EXCLUSION CRITERIA PRIOR TO TRANSPLANT: - Pregnant or lactating females - Hepatitis B with positive viral load prior to transplant conditioning or hepatitis C virus - Human immune deficiency virus - Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent - Creatinine >= 2.0 mg/dL - SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients - Bilirubin >= 3 x ULN (unless Gilbert's syndrome) - Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin - Left ventricular ejection fraction or shortening fraction < 40% - Unlikely to be able to procure additional donor lymphocytes
14 Years - 75 Years
Accepts Healthy Volunteers
Hongtao Liu, ,
University of Chicago
National Cancer Institute (NCI)
Hongtao Liu, Principal Investigator, University of Chicago Comprehensive Cancer Center