Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Bone marrow transplantation; Cytoxan; testosterone cypionate
Intervention description: Infused with non-T-cell depleted bone marrow from a related female donor on Day 0; Cytoxan 50mg/kg IV on Days +3 and +4; testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses)
Intervention MeSH terms: Cyclophosphamide; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Male
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Metastatic Castration-Resistant Prostate Cancer; Bone Marrow Transplantation

Summary:

      Men with progressive metastatic Castration-Resistant Prostate Cancer post first-line
      treatment with either androgen deprivation therapy alone or androgen deprivation therapy plus
      docetaxel who have an identified related female donor (mother sister, daughter, second degree
      relative such as granddaughter or niece) will undergo bone marrow transplantation followed by
      post-transplant Cytoxan (PT/Cy) and testosterone.
    

Eligibility criteria:

        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.