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

Participants undergo total lymphoid irradiation (TLI) on Days -11 to -7 and Days -4 to -1 and receive anti-thymocyte globulin (ATG) per standard institutional practice on Days -11 to -7. Patients also receive oral cyclosporine daily starting on Day -3, and will continue for at least 6 months post-transplant. Patients undergo standard non-myeloablative allogeneic HSCT on Day 0. Patients also receive oral mycophenolate mofetil daily beginning on Day 0 and continuing until Day 28. Participants receive an intravenous infusion of allogeneic cluster of differentiation 8 (CD8)+ memory T-cells over 10 to 20 minutes sometime between day 30 and day 60.

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 standard 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