Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer

Men will undergo pre-transplant screening evaluation and be enrolled in the study. Subjects
will be treated with a standard non-myeloablative conditioning regimen consisting of
Fludarabine 30 mg/m2 IV Days -6 to -2; Cy 14.5 mg/kg IV Days -6 and -5; Total body
irradiation (TBI) 200 cGy Day -1. On Day 0, patients will be infused with non-T-cell depleted
bone marrow from a related female donor. Patients will receive GVHD prophylaxis consisting
of: Cy 50mg/kg IV on Days +3 and +4; tacrolimus (IV or PO) beginning on Day +5 [dose adjusted
to maintain trough level of 5-15 ng/mL] through day+180; Mycophenolate mofetil (MMF) 15 mg/kg
PO TID, with a maximum dose of 1g TID beginning on Day +5 through Day +35. Patients will
receive filgrastim (G-CSF) 5 mcg/kg/day beginning on Day +5 and continued until ANC ≥
1500/mm3. Lastly, to produce maintenance tumor antigen stimulation, patients will be
maintained on continuous LHRH agonist/antagonist therapy (if not previously surgically
castrated) to suppress endogenous testosterone production throughout the treatment period;
testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30
days x 3 doses). Patients who achieve biochemical CR will stop LHRH agonist/antagonist
treatment at day 180. Patients will be followed for 3 years post-BMT.

Inclusion Criteria:

- Performance status ≤1

- Age ≥18 years and ≤ 75 years old

- Histologically-confirmed adenocarcinoma of the prostate

- Treated with continuous androgen ablative therapy (either surgical castration or LHRH
agonist/antagonist) with documented castrate level of serum testosterone (<50 ng/dl)

- Metastatic disease radiographically documented by CT or bone scan

- Patient must be HLA typed at high resolution using DNA based typing at the following
loci: HLA-A, -B, -C, and DRB1

- Patient must have available one or more potential first (biologic mother, sister,
half-sister, or daughter) or second-degree related female donor. Mothers and daughters
have a 100% chance of being haploidentical matches, sisters a 75% chance of being
matched or haploidentical, and second degree relatives have a 50% chance of being
haploidentical matches. The donor and recipient must be HLA identical for at least one
antigen at HLA-A, -B, -C and HLA-DRB1.

- Screening PSA must be ≥ 1.0 ng/mL.

- Prior therapy with one second line hormonal therapy is allowed (i.e. bicalutamide,
nilutamide, flutamide, ketoconazole, abiraterone, enzalutamide, ARN-509).

- Prior docetaxel (≤ 6 cycles) as first line therapy

- Cardiac ejection fraction at rest must be ≥ 40%

- Acceptable liver function: Bilirubin < 2.5 mg/dL (unless due to Gilbert's disease, AST
(SGOT) and ALT (SGPT) < 5 times upper limit of normal.

- Acceptable renal function: Serum creatinine within normal range.

- Pulmonary function: DLCO (corrected for hemoglobin), FEV1 and FVC >50% predicted.

- At least 4 wks since prior radiation or surgery with full recovery (no persistent
toxicity ≥ Grade 1)

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

Exclusion Criteria:

- Prior treatment with Sipuleucel-T, radium-223, strontium-89, or samarium-153

- Prior chemotherapy (docetaxel, cabazitaxel) for castrate resistant prostate cancer

- Evidence of serious and/or unstable pre-existing medical, psychiatric or other
condition (including laboratory abnormalities) that could interfere with patient
safety or provision of informed consent to participate in this study

- Active uncontrolled infection, including known history of HIV/AIDS or hepatitis B or
C.

- Any psychological, familial, sociological, or geographical condition that could
potentially interfere with compliance with the study protocol and follow-up schedule.