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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00086105 | Other Identifier | JHMI-IRB |
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lack of accrual
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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.
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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bone marrow transplantation | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bone marrow transplantation | Procedure | Infused with non-T-cell depleted bone marrow from a related female donor on Day 0 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Prostate-specific Antigen (PSA) Response | 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) | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-related Mortality | Number of participants who experience transplant-related mortality (TRM) following alloBMT | 3 years |
| Number of Participants With a Prostate-specific Antigen Decline ≥ 50% |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Samuel Denmeade, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21205 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Bone marrow transplantation: Infused with non-T-cell depleted bone marrow from a related female donor on Day 0 Cytoxan: Cytoxan 50mg/kg IV on Days +3 and +4 testosterone cypionate: testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 2, 2020 |
Not provided
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| Cytoxan | Drug | Cytoxan 50mg/kg IV on Days +3 and +4 |
|
| testosterone cypionate | Drug | testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses) |
|
|
Proportion of patients achieving a prostate-specific antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria
| 3 years |
| Objective Response Rate or Either Complete Response (CR) or Partial Response (PR) | 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 | 3 years |
| Time to PSA Progression | Time to PSA progression as defined by PCWG2 criteria ( PSA progression as an increase in PSA greater than 25% and >2 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart) | 3 years |
| Time to Clinical/Radiographic Progression | Time to clinical/radiographic progression on CT and bone scan as defined by RECIST ( >=25% increase in PSA from nadir (and by >=2ng/mL), and/or clinical/radiographic progression (clinical progression = symptomatic progression, worsening of disease-related symptoms or new cancer-related complications; radiographic progression on CT scan defined by RECIST 1.1 criteria: >=20% enlargement in sum diameter of soft-tissue target lesions; or on bone scan >=1 new bone lesions), initiation of ADT or death due to any cause, whichever occurs first.) and PCWG2 criteria ( PSA progression as an increase in PSA greater than 25% and >2 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart), respectively. | 3 years |
| Number of Participants Who Experience Acute Graft-versus-host-disease (GVHD) | 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+) | 3 years |
| Number of Participants Who Experience Chronic GVHD | Number of participants who experience chronic GVHD (defined as cGVHD progression while on prednisone at ≥1 mg/kg/day for 1-2 weeks, or stable cGVHD while on ≥0.5 mg/kg/day for 1-2 months, and additional patients remain steroid-dependent with repeated symptom flares during taper of corticosteroids below 0.25 mg/kg/day ) as defined by the protocol. | 3 years |
| Number of Participants With Donor Chimerism | 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. | up to 60 days |
| Number of Participants With Graft Failure | Number of participants with failure to engraft due to rejection by host lymphocytes. | 3 years |
| Effects of Post-transplantation Cyclophosphamide on the Immune Reconstitution of T Cells, B Cells, and NK Cells | The number of participants that have a changed to post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells | 5 years |
| Number of Participants Who Develop HLA Specific Antibodies | Number of participants who develop HLA specific antibodies after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation | 5 years |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Bone marrow transplantation: Infused with non-T-cell depleted bone marrow from a related female donor on Day 0 Cytoxan: Cytoxan 50mg/kg IV on Days +3 and +4 testosterone cypionate: testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Prostate-specific Antigen (PSA) Response | 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) | Posted | Number | percent of participants | 6 months |
|
|
| |||||||||||||||||||||||||||
| Secondary | Transplant-related Mortality | Number of participants who experience transplant-related mortality (TRM) following alloBMT | Posted | Number | participants | 3 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Number of Participants With a Prostate-specific Antigen Decline ≥ 50% | Proportion of patients achieving a prostate-specific antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria | Posted | Count of Participants | Participants | 3 years |
| |||||||||||||||||||||||||||||
| Secondary | Objective Response Rate or Either Complete Response (CR) or Partial Response (PR) | 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 | Posted | Count of Participants | Participants | 3 years |
| |||||||||||||||||||||||||||||
| Secondary | Time to PSA Progression | Time to PSA progression as defined by PCWG2 criteria ( PSA progression as an increase in PSA greater than 25% and >2 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart) | This data was not collected because the study closed before the time to PSA progression could be assessed | Posted | 3 years |
| ||||||||||||||||||||||||||||||
| Secondary | Time to Clinical/Radiographic Progression | Time to clinical/radiographic progression on CT and bone scan as defined by RECIST ( >=25% increase in PSA from nadir (and by >=2ng/mL), and/or clinical/radiographic progression (clinical progression = symptomatic progression, worsening of disease-related symptoms or new cancer-related complications; radiographic progression on CT scan defined by RECIST 1.1 criteria: >=20% enlargement in sum diameter of soft-tissue target lesions; or on bone scan >=1 new bone lesions), initiation of ADT or death due to any cause, whichever occurs first.) and PCWG2 criteria ( PSA progression as an increase in PSA greater than 25% and >2 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart), respectively. | This data was not collected because the study closed before the time to Clinical/radiographic progression could be assessed | Posted | 3 years |
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Acute Graft-versus-host-disease (GVHD) | 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+) | Posted | Count of Participants | Participants | 3 years |
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Experience Chronic GVHD | Number of participants who experience chronic GVHD (defined as cGVHD progression while on prednisone at ≥1 mg/kg/day for 1-2 weeks, or stable cGVHD while on ≥0.5 mg/kg/day for 1-2 months, and additional patients remain steroid-dependent with repeated symptom flares during taper of corticosteroids below 0.25 mg/kg/day ) as defined by the protocol. | Posted | Count of Participants | Participants | 3 years |
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Donor Chimerism | 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. | Posted | Count of Participants | Participants | up to 60 days |
| |||||||||||||||||||||||||||||
| Secondary | Number of Participants With Graft Failure | Number of participants with failure to engraft due to rejection by host lymphocytes. | Posted | Count of Participants | Participants | 3 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Effects of Post-transplantation Cyclophosphamide on the Immune Reconstitution of T Cells, B Cells, and NK Cells | The number of participants that have a changed to post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells | Samples were collected but the tests were not run due to study closure. | Posted | 5 years |
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Develop HLA Specific Antibodies | Number of participants who develop HLA specific antibodies after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation | Samples were collected but the tests were not run due to study closure. | Posted | 5 years |
|
All Adverse events were only collected for the first 6 months. Then for the next 3 year of follow up only transplant-related mortality (TRM) following alloBMT where collected.
There were no serious adverse events for this study
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Bone marrow transplantation: Infused with non-T-cell depleted bone marrow from a related female donor on Day 0 Cytoxan: Cytoxan 50mg/kg IV on Days +3 and +4 testosterone cypionate: testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses) | 0 | 3 | 0 | 3 | 0 | 3 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Samuel R. Denmeade Professor of Oncology| Director Genitourinary Oncology | Johns Hopkins University | 410-502-8341 | DENMESA@jhmi.edu |
| Jul 7, 2022 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D016026 | Bone Marrow Transplantation |
| D003520 | Cyclophosphamide |
| C016131 | testosterone 17 beta-cypionate |
| D013739 | Testosterone |
| ID | Term |
|---|---|
| D016378 | Tissue Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000737 | Androstenols |
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045165 | Testosterone Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
Not provided
Not provided
| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
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