Trial Outcomes & Findings for Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer (NCT NCT02995330)

Results Overview

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)

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

3 participants

Primary outcome timeframe

6 months

Results posted on

2024-02-13

Participant Flow

Participant milestones

Participant milestones
Measure	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)
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bone Marrow Transplantation n=3 Participants 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)
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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)

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Prostate-specific Antigen (PSA) Response	0 percent of participants

SECONDARY outcome

Timeframe: 3 years

Number of participants who experience transplant-related mortality (TRM) following alloBMT

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Transplant-related Mortality	0 participants

SECONDARY outcome

Timeframe: 3 years

Proportion of patients achieving a prostate-specific antigen decline ≥ 50% according to Prostate Cancer Working Group (PCWG2) criteria

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Number of Participants With a Prostate-specific Antigen Decline ≥ 50%	1 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Objective Response Rate or Either Complete Response (CR) or Partial Response (PR)	0 Participants

SECONDARY outcome

Timeframe: 3 years

Population: This data was not collected because the study closed before the time to PSA progression could be assessed

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 3 years

Population: This data was not collected because the study closed before the time to Clinical/radiographic progression could be assessed

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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+)

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Number of Participants Who Experience Acute Graft-versus-host-disease (GVHD)	2 Participants

SECONDARY outcome

Timeframe: 3 years

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.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Number of Participants Who Experience Chronic GVHD	1 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Number of Participants With Donor Chimerism	3 Participants

SECONDARY outcome

Timeframe: 3 years

Number of participants with failure to engraft due to rejection by host lymphocytes.

Outcome measures

Outcome measures
Measure	Bone Marrow Transplantation n=3 Participants 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)
Number of Participants With Graft Failure	0 Participants

SECONDARY outcome

Timeframe: 5 years

Population: Samples were collected but the tests were not run due to study closure.

The number of participants that have a changed to post-transplantation cyclophosphamide on the immune reconstitution of T cells, B cells, and NK cells

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 5 years

Population: Samples were collected but the tests were not run due to study closure.

Number of participants who develop HLA specific antibodies after HLA mismatched, allogeneic partially HLA-mismatched bone marrow transplantation

Outcome measures

Outcome data not reported

Adverse Events

Bone Marrow Transplantation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Samuel R. Denmeade Professor of Oncology| Director Genitourinary Oncology

Johns Hopkins University

Phone: 410-502-8341

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place