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

NCT ID: NCT02995330

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-09
• Study Completion Date: 2021-06-16

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bone marrow transplantation

Intervention Type: PROCEDURE

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

Cytoxan

Intervention Type: DRUG

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

testosterone cypionate

Intervention Type: DRUG

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

Interventions

Bone marrow transplantation

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

Intervention Type: PROCEDURE

Cytoxan

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

Intervention Type: DRUG

testosterone cypionate

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

Intervention Type: DRUG

Other Intervention Names

testosterone

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Denmeade, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00086105

Identifier Type: OTHER

Identifier Source: secondary_id

J1608

Identifier Type: -

Identifier Source: org_study_id