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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01983709
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 44
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Biological: Allogeneic Human Mesenchymal Stem Cells	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of Allogeneic Human Bone Marrow Derived Mesenchymal Stem Cells in Localized Prostate Cancer
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Allogeneic Human Mesenchymal Stem Cells 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. 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.

Biological: Allogeneic Human Mesenchymal Stem Cells; 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.

Outcome Measures

Primary Outcome Measures

1. 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 [Up 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

1. 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.

2. Determine the proportion of MSC to recipient DNA in the peripheral blood [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 peripheral blood.

3. 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.

4. 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.

5. Change in urinary function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy [Baseline to Up to 3 years]

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

6. Change in bowel habits as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy [Baseline to Up to 3 years]

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

7. Change in sexual function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy [Baseline to Up to 3 years]

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

8. Change in hormonal function as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy [Baseline to Up to 3 years]

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

9. Change in overall satisfaction as assessed by the Expanded Prostate Cancer Index Composite (EPIC) survey post-prostatectomy [Baseline 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.

10. Safety as assessed by number of participants experiencing adverse events [Up 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.

11. Safety as assessed by number of participants experiencing serious adverse events [Up 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.

12. Safety as assessed by number of participants experiencing treatment-related adverse events [Up 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21205

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Samuel Denmeade, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT01983709
• Other Study ID Numbers: J1348; NA_00083720
• First Posted: Nov 14, 2013
• Last Update Posted: Jul 16, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

No Results Posted as of Jul 16, 2018