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

NCT02995330 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: J1608IRB00086105
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Metastatic Castration-Resistant Prostate Cancer; Bone Marrow Transplantation

Outcome Measures

Primary Outcomes (1)

• 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)

  6 months

Secondary Outcomes (11)

• Transplant-related Mortality

  3 years

• Number of Participants With a Prostate-specific Antigen Decline ≥ 50%

  3 years

• Objective Response Rate or Either Complete Response (CR) or Partial Response (PR)

  3 years

• Time to PSA Progression

  3 years

• Time to Clinical/Radiographic Progression

  3 years

Study Arms (1)

Bone marrow transplantation

EXPERIMENTAL

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; Drug: Cytoxan; Drug: testosterone cypionate

Interventions

Bone marrow transplantation PROCEDURE

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

Bone marrow transplantation

Cytoxan DRUG

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

Bone marrow transplantation

testosterone cypionate DRUG

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

Also known as: testosterone

Bone marrow transplantation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Bone Marrow Transplantation; Cyclophosphamide; testosterone 17 beta-cypionate; Testosterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Samuel R. Denmeade Professor of Oncology| Director Genitourinary Oncology
• Organization: Johns Hopkins University

DENMESA@jhmi.edu

410-502-8341

Study Officials

• Samuel Denmeade, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 16, 2016
• Study Start: February 9, 2017
• Primary Completion: June 16, 2021
• Study Completion: June 16, 2021
• Last Updated: February 13, 2024
• Results First Posted: February 13, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)