Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

This is a pilot study to assess the safety and potential efficacy of haploidentical
peripheral blood stem cell transplantation using a nonmyeloablative preparative regimen and
post-transplant cyclophosphamide. The overall objective of this study is to collect the
efficacy and safety data to provide the basis to decide whether a larger study of clinical
efficacy is warranted in this setting.

Inclusion Criteria:

Subject

1. Age< 70.

2. Molecular based HLA typing will be performed for the HLA-A, -B, -Cw, DRB1 and -DQB1
loci to the resolution adequate to establish haplo identity. A minimum match of 5/10
is required. An unrelated donor search is not required for a patient to be eligible
for this protocol if the clinical situation dictates an urgent transplant. Clinical
urgency is defined as 6-8 weeks from referral or low-likelihood of finding a matched,
unrelated donor.

3. Subjects must meet one of the disease classifications listed below:

Acute leukemias (includes T lymphoblastic lymphoma). Remission is defined as < 5%
blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a
bone marrow with > 20% cellularity, peripheral blood counts showing ANC >1000/ul,
including patients in CRp.

Acute Lymphoblastic Leukemia in high risk CR1 as defined by at least one of the
following:

Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements White blood
cell counts >30,000/mcL Patients over 30 years of age Time to complete remission >4
weeks Presence of extramedullary disease

Acute Myelogeneous Leukemia in high risk CR1 as defined by at least one of the
following:

Greater than 1 cycle of induction therapy required to achieve remission Preceding
myelodysplastic syndrome (MDS) Presence of Flt3 abnormalities FAB M6 or M7 leukemia or

Adverse cytogenetics for overall survival such as:

those associated with MDS Complex karyotype (≥ 3 abnormalities) Any of the following:
inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities except for
t(8;21), t(9;11), inv(16) or t(16;16)], t(11;19)(q23;p13.1)

Acute Leukemias in 2nd or subsequent remission

Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR.

High-risk MDS status-post cytotoxic chemotherapy

Myelofibrosis

Burkitt's lymphoma: second or subsequent CR.

Lymphoma.

Chemotherapy-sensitive (complete or partial response; see response criteria Appendix
C) large cell, Mantle Cell or Hodgkin's lymphomas that have failed at least 1 prior
regimen of multi-agent chemotherapy and are ineligible for an autologous transplant or
relapsed/progressed after autologous stem cell transplant.

Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at
least two prior therapies (excluding single agent Rituxan) and are ineligible for an
autologous transplant or relapsed/progressed after autologous stem cell transplant..

4. Patients with adequate physical function as measured by:

Cardiac: left ventricular ejection fraction at rest must be ≥ 35%.

Hepatic: bilirubin ≤ 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase < 5 x ULN.

Renal: serum creatinine within normal range for age, or if serum creatinine outside
normal range for age, then renal function(creatinine clearance or GFR) > 40
mL/min/1.73m2.

Pulmonary: FEV1, FVC, DLCO (diffusion capacity) ≥ 40% predicted (corrected for
hemoglobin); if unable to perform pulmonary function tests, then O2 saturation > 92%
on room air.

Performance status: Karnofsky/Lansky score ≥ 60%.

5. Patients who have received a prior allogeneic HSCT and who have either rejected their
grafts or who have become tolerant of their grafts with no active GVHD requiring
immunosuppressive therapy.

Donor

1. Donors must be HLA-haploidentical first-degree or second degree relatives of the
patient.

2. Age ≥ 18 years

3. Weight ≥ 40 kg

Exclusion Criteria:

Subject

1. HLA-matched donor able to donate.

2. Pregnancy or breast-feeding.

3. Current uncontrolled bacterial, viral or fungal infection (currently taking medication
with evidence of progression of clinical symptoms or radiologic findings).

Donor

1) Positive anti-donor HLA antibody.