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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02995330
Recruitment Status : Recruiting
First Posted : December 16, 2016
Last Update Posted : May 16, 2018
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Procedure: Bone marrow transplantation Drug: Bone marrow cell Drug: Cytoxan and testosterone Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Study Start Date : January 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Bone marrow transplantation
Bone marrow transplantation followed by Cytoxan and testosterone
Procedure: Bone marrow transplantation
Bone marrow transplantation followed by post-transplant Cytoxan and testosterone.

Drug: Bone marrow cell
Drug: Cytoxan and testosterone

Primary Outcome Measures :
  1. PSA response [ Time Frame: 5 years ]
    Estimate the percentage of patients with complete biochemical response at 6 months post-transplant (PSA <0.1 ng/mL for patients post-prostatectomy and PSA < 1 ng/mL for patients post-radiation therapy)

Secondary Outcome Measures :
  1. Transplant-related mortality [ Time Frame: 5 years ]
    Estimate the incidence of transplant-related mortality (TRM) following alloBMT

  2. PSA response rate [ Time Frame: 5 years ]
    Estimate PSA response rate [Proportion of patients achieving a PSA decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria]

  3. Objective response rate [ Time Frame: 5 years ]
    Estimate Objective response rate in patients with measurable disease on CT scan using RECIST criteria

  4. Time to PSA progression [ Time Frame: 5 years ]
    Estimate Time to PSA progression based on PCWG2 criteria

  5. Clinical/radiographic progression [ Time Frame: 5 years ]
    Estimate Time to clinical/radiographic progression based upon PCWG2 and RECIST criteria

  6. Incidence of acute graft versus host disease [ Time Frame: 5 years ]
    Assess incidence of acute graft versus host disease grades 2-4 and grades 3-

  7. Incidence of chronic GVHD [ Time Frame: 5 years ]
    Assess incidence of chronic GVHD

  8. Incidence of donor chimerism and graft failure [ Time Frame: 5 years ]
    Assess incidence of donor chimerism and graft failure

  9. Effects of post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells [ Time Frame: 5 years ]
  10. Incidence of HLA specific antibodies [ Time Frame: 5 years ]
    Evaluate incidence of HLA specific antibodies developed after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02995330

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Contact: Connie Collins, RN 410-955-1017
Contact: Rehab AbdAllah 410-955-4042

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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21205
Contact: Connie Collins, RN    410-955-1017   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Principal Investigator: Samuel Denmeade, MD Johns Hopkins University

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Identifier: NCT02995330     History of Changes
Other Study ID Numbers: J1608
IRB00086105 ( Other Identifier: JHMI-IRB )
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: May 16, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Metastatic Castration-Resistant Prostate Cancer
Bone Marrow Transplantation

Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists