Human Telomerase Reverse Transcriptase Messenger RNA (hTERT mRNA) Transfected Dendritic Cell Vaccines

NCT01153113 | Withdrawn Phase 1

• 1 other identifier: LAMP hTERT DC Vaccine
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to develop a new and powerful type of immune therapy for prostate cancer patients. This therapy involves vaccinations with special stimulator cells found in the human body called dendritic cells. These dendritic cells can take up proteins released from cancer cells and present pieces of these proteins to immune cells called T lymphocytes to create a strong stimulatory signal to fight the cancer. One of these proteins is called telomerase, which is found on prostate cancers and is critically important for prostate cancer cells to grow. However, in most cancer patients, the immune system does not adequately destroy the tumor because the T cells are not stimulated sufficiently. T cells require strong stimulation before they grow and become active against cancer cells. We have discovered that substances called ribonucleic acids (RNA), which carry the genetic instructions for the production of telomerase, can be used to overcome this problem and stimulate a strong immune response in cancer patients. In order to test this hypothesis we have designed a clinical study and will enroll patients with metastatic prostate cancer expressing telomerase in order to determine whether or not this vaccine will stimulate T cells, which can recognize and kill prostate tumor cells. The main objectives of this study are to find out whether injections with dendritic cells grown from blood cells and "pulsed" (mixed together for a short period of time) with RNA derived from the patient's own tumor are:

1. 1.Safe without inducing any major side effects.
2. 2.And effective in boosting the patient body's immunity against telomerase expressing prostate cancer cells.
3. 3.Finally, we will test whether or not tumor shrinkage based on serum PSA levels or on X-ray studies will occur.

Conditions

Metastatic Prostate Cancer

Keywords

adenocarcinoma of the prostate; metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+); rising PSA levels while maintained on LHRH analogues

Outcome Measures

Primary Outcomes (1)

• The primary objective of this trial is to evaluate the safety of a boosting regimen using immunizations with two distinct doses of hTERT mRNA DC.

  All subjects will receive 1x107 cells administered ID at study weeks 1, 2, 3, 4, 5, and 6. Subjects will subsequently be randomized with equal probability to receive hTERT mRNA DC at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46, and 50 at one of the following doses: * 5x106 cells per infusion administered ID (Treatment arm A). * 1x107 cells per infusion administered ID (Treatment arm B).

  50 Weeks

Secondary Outcomes (3)

• PSA-specific T cells from pre- and post-therapy PBMC samples

  50 Weeks

• Calculate progression-free survival if subject responds to therapy.

  50 Weeks

• overall survival

  50 Weeks

Study Arms (2)

Treatment Arm A

EXPERIMENTAL

• 5x106 cells per infusion administered ID

Biological: hTERT mRNA DC

Treatment Arm B

EXPERIMENTAL

• 1x107 cells per infusion administered ID (Treatment arm B).

Biological: hTERT mRNA DC

Interventions

hTERT mRNA DC BIOLOGICAL

Subjects receive 1x107 cells per infusion administered ID at study week 1, 2, 3, 4, 5, 6 then receive 5x106 cells per infusion administered ID at study weeks 10, 14, 18, 22, 26, 30, 34, 38, 42, 46 and 50.

Treatment Arm A

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologically or clinically confirmed adenocarcinoma of the prostate with either:
• metastatic prostate adenocarcinoma, Stage (T1-4, N+, M0) or (T1-4, N0-3, M+) OR
• two documented rising PSA levels while maintained on LHRH analogues.
• Subjects who are receiving nonsteroidal antiandrogen therapy must discontinue therapy for 4 weeks prior to study entry.
• Karnofsky Performance Status (KPS) greater than or equal to 80%
• Age ≥ 18 years
• Adequate hematologic function with:
• WBC ≥ 3000 mm3
• hemoglobin ≥ 9 mg/dl
• platelets ≥ 100,000/mm3
• Adequate renal and hepatic function with:
• serum creatinine \< 2.5 mg/dl
• bilirubin \< 2.0 mg/dl
• Adequate coagulation parameters with:
• Prothrombin Time \< 1.5 x control

You may not qualify if:

• Subjects who have received radiation therapy within 4 weeks of pretreatment evaluation. (There must be at least 12 weeks if prior therapy included 89-Strontium between any prior therapy and study entry.)
• Subjects who have received chemotherapy or biologic regimens within 4 weeks of pretreatment evaluation.
• Subjects who have received immunotherapy within 4 weeks of pretreatment evaluation.
• Subjects who have not recovered from radiation, chemotherapy, or immunotherapy toxicities.
• Subjects with either previously irradiated or new CNS (central nervous system) metastases. (Pre-enrollment head CT is not required.)
• Subjects with a history of autoimmune disease such as, but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis.
• Subjects with serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the P.I. to constitute an unwarranted high risk for investigational drug treatment.
• Medical or psychological impediment to probable compliance with the protocol.
• Concurrent second malignancy other than non-melanoma skin cancer, or controlled superficial bladder cancer. In the event of prior malignancies treated surgically, the subject must be considered NED (no evidence of disease) for a minimum of 3 years prior to enrollment.
• Presence of an active acute or chronic infection, including symptomatic urinary tract infection, HIV (as determined by ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and Hepatitis C serology).
• Subjects on steroid therapy (or other immunosuppressive agents such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression. Subjects must have had 4 weeks of discontinuation of any steroid therapy prior to enrollment.

Sponsors & Collaborators

• University of Florida: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: March 31, 2010
• First Posted: June 29, 2010
• Study Start: January 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2010
• Last Updated: December 2, 2011

Record last verified: 2011-02