CD8+ Memory T-Cells as Consolidative Therapy After Donor Non-myeloablative Hematopoietic Cell Transplant in Treating Patients With Leukemia or Lymphoma

PRIMARY OBJECTIVES:

I. To determine the rate of conversion to full donor chimerism (FDC) following a post
transplant infusion (day 30-60) of freshly enriched allogeneic CD8+ memory T-cells in
patients with acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), chronic lymphocytic
leukemia (CLL), or Hodgkin lymphoma (HL), who received non-myeloablative total lymphoid
irradiation (TLI) anti-thymocyte globulin (ATG) transplant conditioning.

SECONDARY OBJECTIVES:

I. To determine the risk of disease progression, overall and event free survival, and
non-relapse mortality.

II. To determine the incidence of acute and chronic graft-versus-host disease (GVHD)
following the infusion of allogeneic CD8+ memory T-cells.

OUTLINE:

Patients undergo TLI on days -11 to -7 and -4 to -1 and receive ATG per standard
institutional practice on days -11 to -7. Patients also receive cyclosporine orally (PO)
daily starting on day -3 and will continue for at least 6 months post-transplant. Patients
undergo non-myeloablative allogeneic hematopoietic stem cell transplant (HSCT) on day 0.
Patients also receive mycophenolate mofetil PO daily beginning on day 0 and continue until
day 28. Based on the patient's status after the initial transplant, patients receive CD8+
memory T-cells intravenously (IV) over 10-20 minutes sometime between day 30 and day 60.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

- Must have a human leukocyte antigen (HLA)-matched or single allele-mismatched adult
sibling serving as donor

- Must have a myeloid or lymphoid malignant disease that is treated with TLI and ATG
reduced intensity conditioning for allogeneic transplant (any of the following AML,
myelodysplastic syndrome [MDS], myeloproliferative disease [MPD], CLL, B or T-cell
NHL, HL)

- Patients who due to age, pre-existing medical conditions, or, prior therapy are
considered to be at high risk for regimen related toxicity associated with fully
ablative transplant conditioning, and therefore reduced intensity conditioning is
recommended

- Ability to understand and the willingness to sign a written informed consent document;
patients must have signed informed consent to participate in the trial

- DONOR: Must be an HLA-matched or single allele mismatched sibling of enrolled
transplant patient

- DONOR: Must be 18-75 years of age, inclusive

- DONOR: Must be in a state of general good health and have completed a donor evaluation
with history, medical examination and standard blood tests within 35 days of starting
the hematopoietic cell collection procedure; in order to fairly represent the
interests of the donor, the donor evaluation and consent will be performed by a study
team member other than the recipient's attending physician

- DONOR: Must have a white blood cell count > 3.5 x 10^9/liter, platelets > 150 x
10^9/liter and hematocrit > 35%

- DONOR: Must be capable of undergoing leukapheresis

- DONOR: Must be able to understand and sign informed consent

- DONOR: Must not be seropositive for HIV 1 and 2, hepatitis B surface antigen,
hepatitis C antibody, human T-lymphotropic virus (HTLV) antibody, cytomegalovirus
(CMV) immunoglobulin M (IgM), or rapid plasma reagin (RPR) (Treponema); donors with
prior evidence of hepatitis B core antibody positivity will have a polymerase chain
reaction (PCR) test done to evaluate for hepatitis B infection; donors with a positive
hepatitis B PCR test are excluded

- DONOR: Females must not be pregnant or lactating

- DONOR: Must not have psychological traits or psychological or medical conditions which
make them unlikely to tolerate the procedure

- DONOR: Must not have developed a new malignancy requiring chemotherapy or radiation in
the interval since apheresis for initial hematocrit (HCT)

- PATIENT CRITERIA FOR PROCEEDING WITH CD8+ MEMORY T-CELL INFUSION:

- Patients must be beyond day 30 and before day 60 after transplant

- Patients must have evidence of mixed CD3 T-cell chimerism based on the day +28 (+/- 7
days) blood sample showing >= 5% and =< 95% donor type cells

- Patients must have no evidence of active graft-versus-host disease at the time of the
CD8+ memory T-cell infusion; patients with a history of acute GVHD overall grade II
based on skin only involvement or upper gastrointestinal (GI) tract involvement only
will be eligible; patients with a history of liver or lower GI tract GVHD will not be
eligible

- Patients must be on single immune suppression therapy with either tacrolimus or
cyclosporine at the time of CD8+ memory T-cell infusion; prednisone at a physiologic
dose of 5 mg per day or less is allowed

- Patients must have a Karnofsky performance status of >= 60% at the time of the CD8+
memory T-cell infusion

- Patients must not have an uncontrolled bacterial, fungal or viral infection, defined
as progressive symptoms despite therapy, at the time of the CD8+ memory T-cell
infusion; asymptomatic viremia is allowed

- Patients must have adequate organ function and performance status at the time of the
CD8+ memory T-cell infusion, defined by the following:

- Total bilirubin =< 4 mg/dL

- SGOT or SGPT =< 4 x ULN

- Creatinine =< 3 mg/dL or estimated creatinine clearance >= 40ml/min

Exclusion Criteria:

- Uncontrolled bacterial, viral or fungal infection defined as currently taking
medication and progression of clinical symptoms

- Progressive hemato-lymphoid malignancy despite conventional therapy

- Acute leukemia not in remission

- Chronic myelogenous leukemia (CML)

- Active central nervous system (CNS) involvement of the underlying malignancy

- Human immunodeficiency virus (HIV) positive

- Pregnant or lactating

- Prior malignancy (EXCEPTION: diagnosed > 5 years ago without evidence of disease, OR
treated =< 5 years ago but have a greater than 50% chance of life expectancy of >= 5
years for that malignancy)

- Have a psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of
the primary physician would place the patient at an unacceptable risk from transplant

- Ejection fraction < 30%, or uncontrolled cardiac failure

- Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% predicted

- Total bilirubin > 3 mg/dL

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
transaminase (SGPT) > 4 x upper limit of normal (ULN)

- Creatinine > 2 mg/dL and an estimated creatinine clearance =< 40 mL/min

- Poorly controlled hypertension despite multiple antihypertensive medication OR

- Karnofsky performance status (KPS) < 60%

- Note: Patients positive for hepatitis B and C will be evaluated on a case by case
basis