Clinical trial NCT02995330
Conditions: Prostate Cancer
Keywords: Metastatic Castration-Resistant Prostate Cancer Bone Marrow Transplantation
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2017-02-09; Completion date: 2021-06-16
Enrollment: 3 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed description:
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.

Arms: arm 1: Bone marrow transplantation followed by Cytoxan and testosterone

Day -6 to -1: Subjects will be treated with a standard non-myeloablative conditioning regimen

Day 0: subjects will be infused with non-T-cell depleted bone marrow from a related female donor.

Subjects will receive GVHD prophylaxis consisting of:

Day +3 and +4: Cytoxan (Cy) 50mg/kg IV Day +5 through Day +180: tacrolimus (IV or PO) beginning \[dose adjusted to maintain trough level of 5-15 ng/mL\] Day +5 through Day +35: Mycophenolate mofetil (MMF) 15 mg/kg PO TID, with a maximum dose of 1g TID.

Day +5: filgrastim (G-CSF) 5 mcg/kg/day, continued until ANC ≥ 1500/mm3.

Day +60, +90, and +120: testosterone cypionate 400 mg IM every 30 days x 3 doses

Subjects will be maintained on continuous LHRH agonist/antagonist therapy (if not previously surgically castrated). Subjects who achieve biochemical CR will stop LHRH agonist/antagonist treatmentat day 180.
Interventions: intervention 1: Bone marrow transplantation intervention 2: Cytoxan intervention 3: testosterone cypionate
Intervention descriptions: intervention 1: Infused with non-T-cell depleted bone marrow from a related female donor on Day 0 intervention 2: Cytoxan 50mg/kg IV on Days +3 and +4 intervention 3: testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses)

Protocol documents:
Prot_SAP_000.pdf: 
NCT02995330