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

Phase 1TerminatedNCT02995330

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins3 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prostate Cancer

Interventions

Bone marrow transplantationPROCEDURE

Infused with non-T-cell depleted bone marrow from a related female donor on Day 0

CytoxanDRUG

Cytoxan 50mg/kg IV on Days +3 and +4

testosterone cypionateDRUG

testosterone cypionate 400 mg IM will be administered on Day +60, +90, and +120 (every 30 days x 3 doses)

Eligibility

Sex: MALEMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

Johns Hopkins Hospital

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

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)

Time frame: 6 months

Secondary Outcomes

Transplant-related Mortality

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

Time frame: 3 years

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

Time frame: 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

Time frame: 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)

Time frame: 3 years

Data from ClinicalTrials.gov

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