Expanded/Activated Gamma Delta T-cell Infusion Following Hematopoietic Stem Cell Transplantation and Post-transplant Cyclophosphamide

Many patients with hematological malignancies require a bone marrow transplant for curative
treatment. A matched sibling donor is optimal but may not be available. Therefore, a
partially matched family member (haploidentical) may be a viable alternative. The incidence
of graft vs. host disease, however, can become more of a significant, even fatal, factor with
partial matches.

T-cells have been shown to be the key player in the post-transplant immune phenomena. The
majority of T-cells are composed of alpha beta T-cells with a small minority of gamma delta
T-cells, which are known to have the unique ability to kill malignant cells without antigen
recognition.

This study proposes to extract, concentrate, and activate gamma delta T-cells from the
peripheral blood to provide innate anti-tumor effect with minimal risk of GVHD. Safety and
impact and/or the rate of GVHD will be evaluated.

Inclusion Criteria:

The following criteria are used to enroll patients in the study before transplant.

- Patients with neoplastic hematological disorders with indication of allogeneic
transplant according to the National Comprehensive Cancer Network (NCCN) or other
standard guidelines as follows:

- Acute myeloid leukemia [AML] in morphologic complete remission with
intermediate/high-risk features (per NCCN criteria) or relapsed disease

- Chronic myeloid leukemia [CML] in any chronic phase.

- Myelodysplastic syndrome [MDS] with intermediate/high risk features or refractory
disease (with bone marrow blast count <10%).

- Acute lymphoblastic leukemia [ALL] in morphologic complete remission with
high-risk features or relapsed disease.

- Negative test for donor-specific antibody within 28 days of starting conditioning
regimen.

- Age Criteria: 19-65 years.

- Organ Function Criteria: The following organ function testing should be done within 35
days before study registration.

- Cardiac: Normal left ventricular ejection fraction (LVEF) (50% or above) as
measured by MUGA or Echocardiogram.

- Pulmonary: FVC, FEV1 and DLCO (corrected) should be 50% or above of expected.

- Renal: serum creatinine level to be <2 mg/dl AND estimated (Cockcroft-Gault
formula) or measured (takes priority if done) creatinine clearance (CrCl) must be
equal or greater than 70 mL/min/1.73 m2.

- Hepatic: serum bilirubin 1.5 upper limit of normal (ULN), Aspartate transaminase
(AST)/alanine transaminase (ALT) 2.5 ULN, and alkaline phosphatase 2.5 ULN.

- Performance status: Karnofsky performance score (KPS) or Lansky score: ≥80.

- Hematopoietic cell transplant comorbidity index (HCT-CI) <3. Exception may be made on
individual cases after discussion with the primary investigator.

- Consent: All patients must be informed of the investigational nature of this study and
given written informed consent in accordance with institutional and federal
guidelines.

The following criteria are required within 48 hours prior to infusion of the EAGD T cell
product.

- Absence of uncontrolled infection with sepsis syndrome (e.g persistent positive blood
culture).

- NO hemodynamic instability (due to sepsis or organ dysfunction) or circulatory volume
overload.

- NO clinically significant organ toxicity that are defined as follows:

- Heart failure with subnormal LVEF or clinical fluid overload.

- Elevated serum creatinine or subnormal creatinine clearance (either estimated or
measured).

- Elevated total bilirubin ≥1.5 upper normal level (unless indirect
hyperbilirubinemia attributed to non-hepatic pathology), or elevated liver
enzymes (ALT, AST, ALP) >5 x ULN.

- Hypoxemia requiring oxygen therapy

- NO acute graft versus host disease (any grade).

- Neutrophil engraftment.

Exclusion Criteria:

- Non-compliant patients.

- No appropriate caregivers identified.

- Uncontrolled medical or psychiatric disorders which may preclude patients to undergo
clinical studies (Discretion of the attending physician).

- Active central nervous system (CNS) neoplastic involvement.

- Morbid obesity with body mass index >35 (borderline cases may be considered on
case-by-case basis after discussion with the primary investigator).

- Patients with known allergy to DMSO.

- HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive.

- Pregnant or breastfeeding women.