Non-myeloablative Allogeneic Transplantation for the Treatment of Multiple Myeloma

Participants are mobilized with cyclophosphamide 4 g/m2 and filgrastim 10 µg/kg/day for
peripheral blood progenitor cell (PBPC) collection by apheresis. Transplant conditioning is
high-dose melphalan 200 mg/m2, followed by PBPC infusion as melphalan rescue [ie, autologous
hematopoietic cells transplant (auto-HCT)]. Post-infusion support includes filgrastim 5
µg/kg/day, starting 6 days following melphalan. Participants with stable or responsive
disease at 4 weeks eligible to continue on to the planned allogenic HCT (allo-HCT). For
allo-HCT, a sibling donor that is fully matched for human leukocyte antigen (HLA-matched) is
identified. Participants receive a single dose of total body irradiation (TBI) 200 centigray
(cGy) as well as immunosuppression with cyclosporine (CSP) 6.25 mg/kg and mycophenolate
mofetil (MMF) 15 mg/kg. The HLA-matched donor begins filgrastim injections 16 µg/kg/day on
day -4 continuing to Day 0, with apheresis collections on Day -1 and Day 0, to a target of >
5 x 10e6 CD34 cells/kg. Allo-HCT is infused to participant on Day 0, with premedication
hydrocortisone 100 mg IV and diphenhydramine 50 mg IV. CSP will be tapered beginning Day 56
with a goal of discontinuing CSP on Day 180, adjusted as needed.

PATIENT INCLUSION CRITERIA

- Multiple myeloma, early Stage II-III or relapsed / progression after initial treatment
of Stage I disease

- Patient has HLA-identical sibling donor

- Age ≤ 70 years

- No prior therapy which would preclude the use of low-dose total body irradiation

- Pathology review and diagnosis confirmation by Stanford University Medical Center

- Karnofsky performance status (KPS) > 70%

- DLCO ≥ 60% predicted

- ALT and AST < 2 x upper limit of normal (ULN)

- Total bilirubin < 2 mg/dL

- Serum creatinine < 2.0, or 24-hour creatinine clearance ≥ 60 mL/min

- HIV-negative

- Signed informed consent document

PATIENT EXCLUSION CRITERIA

- Smoldering multiple myeloma; monoclonal gammopathy of unknown significance; or primary
amyloidosis

- Severe psychological or medical illness

- Prior allogeneic hematopoietic cell transplantation

- Pregnant or lactating

ALLOGENEIC DONOR INCLUSION CRITERIA

- Age ≥ 17

- HIV-seronegative

- Signed informed consent document

ALLOGENEIC DONOR EXCLUSION CRITERIA

- Serious medical or psychological illness

- Pregnant or lactating

- Prior malignancies within the last 5 years, except for non-melanoma skin cancers