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



Status:Recruiting
Conditions:Cancer, Blood Cancer, Blood Cancer, Blood Cancer, Blood Cancer, Lymphoma, Lymphoma, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:18 - 80
Updated:3/21/2019
Start Date:June 2015
End Date:July 2020
Contact:Melanie Gaudinez
Email:mgaudinez@stanford.edu
Phone:650-736-3676

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Post Transplant Infusion of Allogeneic CD8 Memory T-Cells as Consolidative Therapy After Non-myeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Leukemia and Lymphoma

This phase II trial studies how well cluster of differentiation 8 (CD8)+ memory T-cells work
as a consolidative therapy following a donor non-myeloablative hematopoietic cell transplant
in treating patients with leukemia or lymphoma. Giving total lymphoid irradiation and
anti-thymocyte globulin before a donor hematopoietic cell transplant helps stop the growth of
cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells.
When the healthy stem cells from a donor are infused into the patient they may help the
patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.
Sometimes the transplanted cells from a donor can make an immune response against the body's
normal cells (called graft-versus-host disease). Giving cyclosporine and mycophenolate
mofetil after the transplant may stop this from happening. Once the donated stem cells begin
working, the patient's immune system may see the remaining cancer cells as not belonging in
the patient's body and destroy them. Giving an infusion of the donor's white blood cells,
such as CD8+ memory T-cells, may boost this effect and may be an effective treatment to kill
any cancer cells that may be left in the body (consolidative therapy).

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
We found this trial at
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291 Campus Dr
Stanford, California 94305
(650) 725-3900
Principal Investigator: Robert Lowsky
Phone: 650-725-4983
Stanford University School of Medicine Vast in both its physical scale and its impact on...
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