Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

  • Interventional
  • Not Recruiting
  • NCT01839916
Eligibility Details Visit Clinicaltrials.gov

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.

Gender
All

Age Group
14 Years to 75 Years

Accepting Healthy Volunteers?
No

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

At a Glance

National Government IDNCT01839916

IRB#IRB12-1191

Lead SponsorUniversity of Chicago

Lead PhysicianHongtao Liu

Collaborator(s)N/A

EligibilityAll
14 Years to 75 Years
Not Recruiting