- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02995330
Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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-
Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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. |
Infused with non-T-cell depleted bone marrow from a related female donor on Day 0
Cytoxan 50mg/kg IV on Days +3 and +4
testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prostate-specific Antigen (PSA) Response
Time Frame: 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)
|
6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Transplant-related Mortality
Time Frame: 3 years
|
Number of participants who experience transplant-related mortality (TRM) following alloBMT
|
3 years
|
Number of Participants With a Prostate-specific Antigen Decline ≥ 50%
Time Frame: 3 years
|
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)
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
|
3 years
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Time to PSA Progression
Time Frame: 3 years
|
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 Frame: 3 years
|
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)
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+)
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3 years
|
Number of Participants Who Experience Chronic GVHD
Time Frame: 3 years
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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.
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3 years
|
Number of Participants With Donor Chimerism
Time Frame: up to 60 days
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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.
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up to 60 days
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Number of Participants With Graft Failure
Time Frame: 3 years
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Number of participants with failure to engraft due to rejection by host lymphocytes.
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3 years
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Effects of Post-transplantation Cyclophosphamide on the Immune Reconstitution of T Cells, B Cells, and NK Cells
Time Frame: 5 years
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The number of participants that have a changed to post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells
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5 years
|
Number of Participants Who Develop HLA Specific Antibodies
Time Frame: 5 years
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Number of participants who develop HLA specific antibodies after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation
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5 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Samuel Denmeade, MD, Johns Hopkins University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Androgens
- Anabolic Agents
- Cyclophosphamide
- Testosterone
- Methyltestosterone
- Testosterone undecanoate
- Testosterone enanthate
- Testosterone 17 beta-cypionate
Other Study ID Numbers
- J1608
- IRB00086105 (Other Identifier: JHMI-IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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