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Allogeneic Human Bone Marrow Derived Mesenchymal Stem Cells in Localized Prostate Cancer

Phase 1
Terminated
Conditions
Prostate Cancer
Interventions
Biological: Allogeneic Human Mesenchymal Stem Cells
Registration Number
NCT01983709
Lead Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Brief Summary

The objective of this study is to determine if systemically infused allogeneic bone marrow derived mesenchymal stem cells (MSC) home to sites of prostate cancer in men with localized adenocarcinoma of the prostate that are planning to undergo a prostatectomy. Investigators plan to systemically infuse MSCs 4, 6 or 8 days prior to enrolled subjects' planned prostatectomies. Investigators will then quantify the relative amount of donor MSC DNA to recipient DNA present in patients' explanted prostate specimens. This will be accomplished via BEAMing digital PCR. This trial will provide the foundation for future studies aimed at engineering MSCs to deliver a toxin to sites of metastatic prostate cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
Male
Target Recruitment
7
Inclusion Criteria

(MSC donor cohort):

  1. Age ≥18 years, ≤30 years
  2. Male sex
  3. Donor must meet the selection and eligibility criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT) and FDA 21 CFR Part 1271
Exclusion Criteria

(MSC donor cohort):

  1. 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.
  2. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  3. Inability to provide informed consent.

MSC Recipients

Inclusion Criteria (Treatment cohort):

  1. Age ≥18 years
  2. Eastern cooperative group (ECOG) performance status ≤2
  3. Documented histologically confirmed adenocarcinoma of the prostate
  4. Gleason score on diagnostic biopsy specimens of ≥ 6
  5. ≥ 3 positive cores within diagnostic biopsy specimens
  6. At least one prostate core must contain ≥ 30% prostate cancer
  7. Scheduled to undergo a prostatectomy at Johns Hopkins
  8. Has not received systemic therapy for prostate cancer (i.e. LHRH agonist/antagonist therapy)
  9. Sexual Health Inventory in Men (SHIM) score ≥ 17

Exclusion Criteria (Treatment cohort):

  1. Prior radiation therapy to the prostate.
  2. 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.
  3. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
  4. Inability to provide informed consent.
  5. Any active autoimmune disease requiring treatment (e.g. steroid, disease-modifying antirheumatic drugs, biologic agents, etc.).
  6. Prior history of penicillin or streptomycin allergy.
  7. No prior history of deep venous thrombosis or pulmonary embolism within 5 years prior to enrollment in the study.
  8. Abnormal liver function (bilirubin, AST, ALT ≥ 3 x upper limit of normal)
  9. Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
  10. Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years prior to enrollment in the study.
  11. History of symptomatic pulmonary dysfunction.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Allogeneic Human Mesenchymal Stem CellsAllogeneic Human Mesenchymal Stem CellsThis will be a dose escalation study. The first 3 subjects will receive a single dose of 1 x 10\^6 cells/kg or a maximum dose of 1 x 10\^8 total cells IV. The remaining subjects will receive a single dose of 2 x 10\^6 cells/kg or a maximum dose of 2 x 10\^8 total cells IV.
Primary Outcome Measures
NameTimeMethod
Amount of systemically infused (MSC) DNA relative to recipient DNA at sites of prostate cancer in men with localized adenocarcinoma of the prostate that are scheduled to undergo a prostatectomyUp to 3 years

Allogeneic MSCs will be quantified through tissue BEAMing and the percent of MSCs per total cell number will be calculated.

Secondary Outcome Measures
NameTimeMethod
Determine the proportion of MSC to recipient DNA within the seminal vesicle.Up to 3 years

Proportion of MSC to recipient DNA is calculated by number of MSCs over the number of recipient DNA (\[number of MSC\]/\[number of recipient DNA\]) in the seminal vesicle.

Change in bowel habits as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomyBaseline to Up to 3 years

Change in total bowel habits score (possible score range from 8-62) on the EPIC survey.

Change in hormonal function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomyBaseline to Up to 3 years

Change in total hormonal function score (possible score range from 5-49) on the EPIC survey.

Change in overall satisfaction as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomyBaseline to Up to 3 years

Change in overall satisfaction score (possible score range from 1-5) on the EPIC survey with a higher score reflecting higher overall satisfaction.

Safety as assessed by number of participants experiencing treatment-related adverse eventsUp to 3 years

Number of participants experiencing treatment-related adverse events as defined by the revised National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.0 published 14 June 2010.

Feasibility of infusing MSCs into men with localized prostate cancer who plan to undergo a prostatectomy.Up to 3 years

The percentage of screened subjects that agreed to receive a pre-prostatectomy infusion of MSCs at the pre-specified time point and subsequently undergo a radical prostatectomy.

Changes in the Sexual Health Inventory for Men (SHIM) survey post-prostatectomy.Up to 3 years

The SHIM is a measure of sexual function with a score ranging from 1 (severe erectile dysfunction) to 25 (normal function). Participants are required to have a score of \>=17 to be eligible for the study.

Safety as assessed by number of participants experiencing serious adverse eventsUp to 3 years

Number of participants experiencing serious adverse events as defined by the revised National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.0 published 14 June 2010.

Determine the proportion of MSC to recipient DNA in the peripheral bloodUp to 3 years

Proportion of MSC to recipient DNA is calculated by number of MSCs over the number of recipient DNA (\[number of MSC\]/\[number of recipient DNA\]) in the peripheral blood.

Change in urinary function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomyBaseline to Up to 3 years

Change in total urinary function score (possible score range from 5-51) on the EPIC survey.

Safety as assessed by number of participants experiencing adverse eventsUp to 3 years

Number of participants experiencing adverse events as defined by the revised National Cancer Institute Common Toxicity Criteria (NCI CTC), version 4.0 published 14 June 2010.

Change in sexual function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomyBaseline to Up to 3 years

Change in total sexual function score (possible score range from 10-61) on the EPIC survey.

Trial Locations

Locations (1)

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

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