Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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.
 
ClinicalTrials.gov Identifier: NCT02995330
Recruitment Status : Recruiting
First Posted : December 16, 2016
Last Update Posted : May 13, 2019
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE December 14, 2016
First Posted Date  ICMJE December 16, 2016
Last Update Posted Date May 13, 2019
Actual Study Start Date  ICMJE February 9, 2017
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
PSA response [ Time Frame: 6 months ]
Percentage of participants 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)
Original Primary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
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)
Change History Complete list of historical versions of study NCT02995330 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • Transplant-related mortality [ Time Frame: 3 years ]
    Number of participants who experience transplant-related mortality (TRM) following alloBMT
  • PSA response rate [ Time Frame: 3 years ]
    Proportion of patients achieving a PSA decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria
  • Objective response rate [ Time Frame: 3 years ]
    Percentage of participants with reduction in measurable disease on CT scan as defined by RECIST criteria: Complete Response (CR)= disappearance of all target lesions; Partial Response (PR)= at least a 30% decrease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD)= at least 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable disease (SD)= Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
  • Time to PSA progression [ Time Frame: 3 years ]
    Time to PSA progression as defined by PCWG2 criteria
  • Time to Clinical/radiographic progression [ Time Frame: 3 years ]
    Time to clinical/radiographic progression on CT and bone scan as defined by RECIST and PCWG2 criteria, respectively.
  • Number of participants who experience acute graft-versus-host-disease (GVHD) [ Time Frame: 3 years ]
    Number of participants with acute GVHD grades 2-4 and grades 3-4 as defined by Przepiorka criteria. Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+)
  • Number of participants who experience chronic GVHD [ Time Frame: 3 years ]
    Number of participants who experience chronic GVHD as defined by protocol.
  • Number of participants with donor chimerism [ Time Frame: up to 60 days ]
    Patients with any amount of donor chimerism around day 60 will be considered as having engrafted. Chimerism determinations will be made on peripheral blood by a number of different methods depending on the specific patient. Methods may include (i) the usual standard of restriction fragment length polymorphism (RFLP) if the donor and recipient RFLPs are informative, (ii) fluorescence in-situ hybridization (FISH) for Y-chromosome markers on PBMC if the donor is male, (iii) cytogenetic analysis, (iv) flow cytometric analysis of HLA-A, B or DR on lymphocytes in the peripheral blood if haploidentical and suitable reagents exist or (v) PCR analysis of variable nucleotide tandem repeats (VNTR) in PBMC if informative. Mixed donor chimerism will be defined as >0%, but <95%. Complete donor chimerism will be defined as >95%. Patients who have relapsed or died prior to day 60 will not be evaluable for full donor chimerism, as these are competing risk factors.
  • Number of participants with graft failure [ Time Frame: 3 years ]
    Number of participants with failure to engraft due to rejection by host lymphocytes.
  • Effects of post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells [ Time Frame: 5 years ]
  • Number of participants who develop HLA specific antibodies [ Time Frame: 5 years ]
    Number of participants who develop HLA specific antibodies after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation
Original Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2016)
  • Transplant-related mortality [ Time Frame: 5 years ]
    Estimate the incidence of transplant-related mortality (TRM) following alloBMT
  • 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]
  • Objective response rate [ Time Frame: 5 years ]
    Estimate Objective response rate in patients with measurable disease on CT scan using RECIST criteria
  • Time to PSA progression [ Time Frame: 5 years ]
    Estimate Time to PSA progression based on PCWG2 criteria
  • Clinical/radiographic progression [ Time Frame: 5 years ]
    Estimate Time to clinical/radiographic progression based upon PCWG2 and RECIST criteria
  • 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-
  • Incidence of chronic GVHD [ Time Frame: 5 years ]
    Assess incidence of chronic GVHD
  • Incidence of donor chimerism and graft failure [ Time Frame: 5 years ]
    Assess incidence of donor chimerism and graft failure
  • Effects of post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells [ Time Frame: 5 years ]
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Official Title  ICMJE A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Procedure: Bone marrow transplantation
    Infused with non-T-cell depleted bone marrow from a related female donor on Day 0
  • Drug: Cytoxan
    Cytoxan 50mg/kg IV on Days +3 and +4
  • Drug: testosterone cypionate
    testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses)
    Other Name: testosterone
Study Arms  ICMJE Experimental: 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.

Interventions:
  • Procedure: Bone marrow transplantation
  • Drug: Cytoxan
  • Drug: testosterone cypionate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 15, 2016)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Connie Collins, RN 410-955-1017 ccolli23@jhmi.edu
Contact: Rehab AbdAllah 410-955-4042 rabdall1@jhmi.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02995330
Other Study ID Numbers  ICMJE J1608
IRB00086105 ( Other Identifier: JHMI-IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Samuel Denmeade, MD Johns Hopkins University
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP