Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

Patients who receive an allogeneic (using another person as the donor) stem cell transplant
(SCT) are at risk for developing graft-versus-host disease (GVHD).

The word "graft" refers to the donor blood cells that you will receive during the transplant.
The word "host" refers to the person receiving the cells. GVHD is a complication of
transplantation where the donor graft attacks and damages some of the participant's tissues.

GVHD may occur when the T cells (a type of white blood cell that helps protect the body from
infection) from the donor react against normal tissues or organs in the body. There are two
basic types of GVHD:

- Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin,
gastrointestinal tract (stomach and intestines) and liver.

- Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many
organs and significantly diminish quality of life.

To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a
biopsy (a small sample of the participant's tissue to look at under the microscope) of the
skin, gut, or, rarely, the liver.

In this research study, the investigator are investigating a pre-transplant intervention
aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β
Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR)
α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to
the participant. By selectively removing this specific type of T cells from the donor
product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of
the transplant.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
studied.

The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell
depletion system for use in the US, but this system is approved by the European Medicines
Agency (EMA) and used in Europe

Inclusion Criteria:

- Diagnoses and stage at time of transplant admission:

- Acute leukemia (AML or ALL or MPAL) in first or subsequent remission

- Myelodysplastic syndromes (MDS) with <10% marrow blasts

- Myeloproliferative neoplasm (MPN) with <10% marrow blasts

- CMML with less than 10% marrow blast

- CML accelerated phase or second or subsequent chronic phase

- Non-Hodgkin's lymphoma in PR or CR2 or beyond

- Hodgkin lymphoma in PR or CR2 or beyond

- Age 18-65 years

- Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C,
DRB1 and DQB1, based on allele level typing.

- Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)

- Patient deemed to be appropriate candidate for myeloablative conditioning
transplantation.

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patient with active HIV infection

- Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)

- Prior allogeneic hematopoietic stem cell transplantation

- Impaired cardiac function- ejection fraction < 40%

- Impaired pulmonary function- pretransplant FEV1, DLCO < 50%

- Impaired renal function, based on

--Serum creatinine > 2.0 mg/dl

- Impaired liver function unrelated to primary disease, based on

--ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or
suspected Gilbert's disease)

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Women who are pregnant or breast feeding. Women of child bearing potential must have a
negative serum pregnancy test at study entry.

- Participants who are receiving any other investigational agents are eligible but such
agent must be discontinued before admission for HSCT, and if resumption of
investigation agent is planned after HSCT, this must be approved by the study PI.

- Participants with known active CNS disease. CNS disease that has been treated is
eligible