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

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.

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