Clinical trial NCT02995330: Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Official title: A Pilot Study of Sex-Mismatched Allogeneic Bone Marrow Transplantation for Men With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: Metastatic Castration-Resistant Prostate Cancer
Bone Marrow Transplantation
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
First posted: 2016-12-16
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prostate-specific Antigen (PSA) Response
timeFrame: 6 months
Secondary outcomes:
measure: Transplant-related Mortality
timeFrame: 3 years
measure: Number of Participants With a Prostate-specific Antigen Decline ≥ 50%
timeFrame: 3 years
measure: Objective Response Rate or Either Complete Response (CR) or Partial Response (PR)
timeFrame: 3 years
measure: Time to PSA Progression
timeFrame: 3 years
measure: Time to Clinical/Radiographic Progression
timeFrame: 3 years
measure: Number of Participants Who Experience Acute Graft-versus-host-disease (GVHD)
timeFrame: 3 years
measure: Number of Participants Who Experience Chronic GVHD
timeFrame: 3 years
measure: Number of Participants With Donor Chimerism
timeFrame: up to 60 days
measure: Number of Participants With Graft Failure
timeFrame: 3 years
measure: Effects of Post-transplantation Cyclophosphamide on the Immune Reconstitution of T Cells, B Cells, and NK Cells
timeFrame: 5 years
measure: Number of Participants Who Develop HLA Specific Antibodies
timeFrame: 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Samuel Denmeade, MD
role: PRINCIPAL_INVESTIGATOR
References: