A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Prostate-specific Antigen (PSA) Response
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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-DRB
- •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.
排除标准
- •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.
研究组 & 干预措施
Bone marrow transplantation
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.
干预措施: Bone marrow transplantation (Procedure)
Bone marrow transplantation
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.
干预措施: Cytoxan (Drug)
Bone marrow transplantation
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.
干预措施: testosterone cypionate (Drug)
结局指标
主要结局
Prostate-specific Antigen (PSA) Response
时间窗: 6 months
Percentage of participants with complete biochemical response at 6 months post-transplant (prostate-specific antigen \<0.1 ng/mL for patients post-prostatectomy and prostate-specific antigen\< 1 ng/mL for patients post-radiation therapy)
次要结局
- Number of Participants Who Experience Chronic GVHD(3 years)
- Time to PSA Progression(3 years)
- Transplant-related Mortality(3 years)
- Number of Participants With a Prostate-specific Antigen Decline ≥ 50%(3 years)
- Number of Participants With Graft Failure(3 years)
- Objective Response Rate or Either Complete Response (CR) or Partial Response (PR)(3 years)
- Effects of Post-transplantation Cyclophosphamide on the Immune Reconstitution of T Cells, B Cells, and NK Cells(5 years)
- Time to Clinical/Radiographic Progression(3 years)
- Number of Participants Who Experience Acute Graft-versus-host-disease (GVHD)(3 years)
- Number of Participants With Donor Chimerism(up to 60 days)
- Number of Participants Who Develop HLA Specific Antibodies(5 years)