Plerixafor and Sargramostim (GM-CSF) for Mobilization of Allogeneic Sibling Donors

The main purpose of this study is to gather information about the combination the drugs
plerixafor with sargramostim in donors of blood-forming cells (stem cells). Stem cells can
be taken from the bone marrow of the pelvic bones or from the blood following treatment with
drugs called growth factors; sargramostim is such a drug. Once stem cells leave the bone
marrow and circulate in the blood, they are called peripheral blood stem cells (PBSCs).
These cells can be collected through a routine procedure called apheresis, which involves
placing two IVs into the arm which are connected to an apheresis machine; the machine then
takes blood from the body, removes the stem cells, and returns the blood to the body.

Normally, a growth factor called filgrastim is given to donors in order to collect the stem
cells used for transplantation. However, when stem cells collected using filgrastim are
transplanted in patients, a possible unpredictable complication is graft versus host
disease. It's thought that using a different growth factor such as sargramostim might reduce
the occurrences of graft versus host disease in patients. However, sargramostim alone does
not provide as many stem cells for transplantation as other growth factors. Plerixafor is
another drug that can increase the number of PBSCs in a donor, but like with sargramostim,
plerixafor alone does not always provide enough stem cells. This is why sargramostim and
plerixafor are being combined in this study: the investigators believe that the two drugs
together will provide enough stem cells for transplantation and may also reduce the risk of
graft versus host disease.

Inclusion Criteria:

Donor Eligibility

- Donor is 18 to 65 years of age inclusive.

- If female and of child-bearing age, donor must be non-pregnant, not breastfeeding,
and agree to use adequate contraception.

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

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

- Donor has adequate renal function as defined by a calculated serum creatinine
clearance of ≥56 ml/min for females and ≥64 ml/min for males.

- Donor has adequate hepatic function as defined by a total bilirubin <2x normal or
absence of hepatic fibrosis/cirrhosis.

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

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

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

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

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

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

- Donor is not currently enrolled on another investigational agent study.

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

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

Recipient Eligibility

- Recipient must have available the successful collection of a GM-CSF + plerixafor
mobilized product. When an adequate collection cannot be obtained, G-CSF will be used
and some recipients may need to receive a combined product of mobilized cells with
plerixafor + GM-CSF and G-CSF mobilized cells. Recipients who receive less than 2.0 X
106 CD34+ cells/kg/actual recipient weight after six days of GM-CSF and two days of
IV plerixafor will not be considered "eligible" but followed per protocol for safety
purposes only.

- Recipient is 18 to 65 years of age inclusive.

- Recipient is willing and has a 6/6 HLA-matched sibling willing to donate PBSC for
transplant.

- Recipient must provide signed informed consent.

- If female and of child-bearing age, recipient must be non-pregnant, not
breastfeeding, and using adequate contraception.

- Recipient must have one of the following diagnoses:

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

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

- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the
International Prognostic Scoring System,

- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase,

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

- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior
regimens, OR

- Multiple myeloma (MM), Stage 2-3.

- Myeloproliferative disorder or neoplasm

- 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% of predicted and a DLCO ≥40% of predicted, corrected for
hemoglobin.

- Recipient must have adequate renal function as defined by a serum creatinine
clearance (Cockcroft-Gault equation)of ≥56 ml/min for females and ≥64 ml/min for
males of normal

- Recipient must have adequate hepatic function as defined by a total bilirubin <2x
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 have no evidence of active infection at the time of the transplant
preparative regimen or at time of transplantation.

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

- Recipient has an ECOG performance status of 0 or 1.

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

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

- Recipient must not be enrolled on another investigational agent concurrently.

- Recipient must not have any medical condition, which, in the opinion of the clinical
investigator, would interfere with the evaluation of the patient.

- Recipient must have a life expectancy of greater than 4 weeks.

- Both men and women and members of all races and ethnic groups are eligible for this
trial.

Exclusion Criteria:

Donor Exclusion Criteria in addition to that stated above

- Donor may not be receiving any other investigational agents.

- Donor may not have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to plerixafor or GM-CSF, or known hypersensitivity
to yeast-derived products or any component of the product.