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 : February 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer||Procedure: Bone marrow transplantation Drug: Cytoxan Drug: testosterone cypionate||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer|
|Actual Study Start Date :||February 9, 2017|
|Estimated Primary Completion Date :||January 2023|
|Estimated Study Completion Date :||January 2025|
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.
Procedure: Bone marrow transplantation
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
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
- 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)
- 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
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 ClinicalTrials.gov identifier (NCT number): NCT02995330
|Contact: Connie Collins, RNfirstname.lastname@example.org|
|Contact: Rehab AbdAllahemail@example.com|
|United States, Maryland|
|Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Connie Collins, RN 410-955-1017 firstname.lastname@example.org|
|Principal Investigator:||Samuel Denmeade, MD||Johns Hopkins University|