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

Phase 1TerminatedNCT01983709

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins7 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prostate Cancer

Interventions

This 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 4 days prior to undergoing a planned prostatectomy. 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 either 4 or 6 days prior to the planned prostatectomy, and if additional doses of MSCs are able to be expanded, up to 6 additional men will be enrolled with a plan to treat them 8 days prior to the prostatectomy.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 YearsHealthy volunteers:

Medical Language ↔ Plain English

MSC Donors 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.

Outcomes

Primary Outcomes

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 prostatectomy

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

Time frame: Up to 3 years

Secondary Outcomes

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

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.

Time frame: Up to 3 years

Determine the proportion of MSC to recipient DNA in the peripheral blood

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.

Time frame: Up to 3 years

Determine the proportion of MSC to recipient DNA within the seminal vesicle.

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.

Time frame: Up to 3 years

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

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.

Time frame: Up to 3 years

Change in urinary function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy

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