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.
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.
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.
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.
14 Years to 75 Years
Accepting Healthy Volunteers?
- 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 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