Safety and Efficacy of POL6326 for Mobilization/Transplant of Sibling Donor in Patients With Hematologic Malignancies

Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling
donors. This process requires from four to six days of G-CSF injection and is associated
with significant morbidity, most notably bone pain. POL6326 is associated with few side
effects and collection of cells occurs on the same day as POL6326 administration.

This study will evaluate the safety and efficacy of this novel agent for hematopoietic
progenitor cell mobilization and allogeneic transplantation based on the following
hypotheses:

1. Donors mobilized with intravenous POL6326 will require fewer collections than have
previously been seen for donors mobilized with subcutaneous plerixafor.

2. Healthy HLA-matched donors receiving one or two infusions of POL6326 will mobilize
sufficient CD34+ cells (at least 2.0 x 106 CD34+ cells/kg recipient weights) following
leukapheresis to support a hematopoietic cell transplant.

3. IV POL6326 will result in more rapid kinetics and a higher maximum (peak) of human
CD34+ stem cells mobilized from human normal allogeneic donors compared to previous
donors who were mobilized with plerixafor.

4. The hematopoietic cells mobilized by IV POL6326 will be functional and will result in
prompt and durable hematopoietic engraftment following transplantation into
HLA-identical siblings with advanced hematological malignancies using various
non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD
prophylaxis.

Donor Inclusion Criteria

- Donor must be 18 to 70 years of age inclusive.

- Donor must be a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

- Donor must have adequate cardiac function with no history of congestive heart failure
and no history of atrial fibrillation or ventricular tachyarrhythmia.

- Donor must have adequate renal function as defined by a minimum creatinine clearance
(CrCl) value of >30 ml/min.

- Donor must have adequate hepatic function as defined by a total bilirubin <3x upper
limit of normal.

- Donor must have adequate neurologic function as defined by NO evidence of a severe
central or peripheral neurologic abnormality and no history of cerebrovascular
accident or seizure disorder requiring anticonvulsant medication.

- Donor must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed
test.

- Donor must have an ECOG performance status of 0 or 1.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.

- Donor must demonstrate ability to be compliant with study regimen.

- Donor must be able to understand and willing to sign an IRB approved written informed
consent document.

Recipient Inclusion Criteria

- Recipient must have available the successful collection of a POL62326 mobilized
product.

- Recipient must be 18 to 75 years of age inclusive.

- Recipient must have a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.

- Recipient must have one of the following diagnoses:

- Acute myelogenous leukemia (AML) in 1st or subsequent remission

- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission

- Chronic myelogenous leukemia (CML)

- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete
remission, partial remission

- Chronic lymphocytic leukemia (CLL)

- Multiple myeloma (MM)

- Myelodysplastic syndrome (MDS)

- Myeloproliferative disorder (MPD)

- Recipient must have adequate cardiac function with a left ventricular ejection
fraction > 40%.

- Recipient must have adequate pulmonary function defined as NO severe or symptomatic
restrictive or obstructive lung disease, and formal pulmonary function testing
showing an FEV1 >50% (predicted) and a DLCO >40% (predicted), corrected for
hemoglobin.

- Recipient must have adequate hepatic function as defined by a total bilirubin <3x
upper limit of normal or absence of hepatic fibrosis/cirrhosis.

- Recipient must have adequate neurologic function as defined by NO evidence of a
severe central or peripheral neurologic abnormality. Patients with a history of
previous CNS tumor involvement are eligible provided they are without symptoms or
signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain.

- Recipient must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA
licensed test.

- Recipient must have an ECOG performance status of 0 or 1.

- Recipient must demonstrate ability to be compliant with medical regimen.

- Recipient must have life expectancy of greater than 2 months.

- Recipient must be able to understand and willing to sign an IRB approved written
informed consent document.

Donor Exclusion Criteria

- Donor must not have an active infection at the time of study entry.

- Donor must not have active alcohol or substance abuse within 6 months of study entry.

- Donor must not be currently enrolled on another investigational agent study.

- Donor must not have any medical condition, which, in the opinion of the clinical
investigator, would interfere with his/her evaluation.

- Donor must not have an 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.

- If female and of child-bearing age, donor must not be pregnant or breastfeeding.

Recipient Exclusion Criteria

- Recipient must not have had (the following therapies within the following timeframe):

- Investigative drugs within 21 days

- Recipient must have no evidence of active infection at the time of the transplant
preparative regimen or at time of transplantation.

- Recipient must have no active alcohol or substance abuse within 6 months of study
entry.

- Recipient must not be pregnant and/or breastfeeding.