MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer

• ClinicalTrials.gov Identifier: NCT00868595
• Recruitment Status: Completed
• First Posted: March 25, 2009
• Last Update Posted: October 8, 2019
• Sponsor: Bellicum Pharmaceuticals
• Collaborators: M.D. Anderson Cancer Center; The University of Texas Health Science Center, Houston; Memorial Hermann Hospital; Baylor College of Medicine
• Information provided by (Responsible Party): Bellicum Pharmaceuticals

Tracking Information

• First Submitted Date: March 24, 2009
• First Posted Date: March 25, 2009
• Last Update Posted Date: October 8, 2019
• Study Start Date: April 2009
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 5, 2017)

• Maximum tolerated dose of BPX-101 and AP1903 [ Time Frame: 1 Year ]
  To determine the maximum tolerated dose (MTD) of BPX-101 and AP1903 when administered 24 hours apart
• Safety and tolerability of BPX-101 and AP1903 [ Time Frame: 1 Year ]
  To determine other measures of safety and tolerability of BPX-101 and AP1903 when administered 24 hours apart to patients with castrate resistant prostate cancer (CRPC).

Original Primary Outcome Measures (submitted: March 24, 2009)

• To determine the maximum tolerated dose (MTD) of BP-GMAX-CD1 and AP1903 when administered 24 hours apart [ Time Frame: 1 Year ]
• To determine other measures of safety and tolerability of BP-GMAX-CD1 and AP1903 when administered 24 hours apart to patients with androgen-independent prostate cancer (AIPC) [ Time Frame: 1 Year ]

Current Secondary Outcome Measures (submitted: December 5, 2017)

• Pharmacokinetics of AP1903 [ Time Frame: 1 Year ]
  To determine the pharmacokinetics of AP1903 when administered 24 hours after BPX-101
• Immune responses and their association with clinical outcome [ Time Frame: 2 Years ]
  To assess immune responses and their association with clinical outcome as measured by changes in levels of interferon gamma (IFN)-producing T cells, the cytotoxic T lymphocyte (CTL) response, cytokines (IFN, IL-4, IL-10), activation markers, and other markers
• PSA response and PSA dynamics [ Time Frame: 1 Year ]
  To assess PSA response and PSA dynamics (change in velocity, doubling time)
• Number of circulating tumor cells (CTC) [ Time Frame: 1 Year ]
  To assess reduction in the number of circulating tumor cells (CTC)
• Cancer-related pain [ Time Frame: 1 Year ]
  To assess cancer-related pain
• Pain medication usage [ Time Frame: 1 Year ]
  To assess pain medication usage
• Preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD) [ Time Frame: 2 Years ]
  To determine preliminary efficacy of BPX-101 at the maximum tolerated dose (MTD), based on tumor assessments using computed tomography (CT) or magnetic resonance imaging (MRI) and radionuclide bone scans

Original Secondary Outcome Measures (submitted: March 24, 2009)

• To determine the pharmacokinetics of AP1903 when administered 24 hours after BP-GMAX-CD1 [ Time Frame: 1 Year ]
• To assess immune responses and their association with clinical outcome as measured by changes in levels of interferon gamma (IFN)-producing T cells, the cytotoxic T lymphocyte (CTL) response, cytokines (IFN, IL-4, IL-10), activation markers, and other [ Time Frame: 2 Years ]
• To assess PSA response and PSA dynamics (change in velocity, doubling time) [ Time Frame: 1 Year ]
• To assess reduction in the number of circulating tumor cells (CTC) [ Time Frame: 1 Year ]
• To assess cancer-related pain [ Time Frame: 1 Year ]
• To assess pain medication usage [ Time Frame: 1 Year ]
• To determine preliminary efficacy of BP-GMAX-CD1 at the maximum tolerated dose (MTD), based on tumor assessments using computed tomography (CT) or magnetic resonance imaging (MRI) and radionuclide bone scans [ Time Frame: 2 Years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MTD Study of Vaccine BP-GMAX-CD1 Plus AP1903 to Treat Castrate Resistant Prostate Cancer
• Official Title: A Phase I, Non-randomized, Multiple Dose, Dose Escalation Study of the Safety, PK, PD and Efficacy of Therapeutic Vaccine, BP-GMAX-CD1, Plus Activating Agent, AP1903, in Patients With Castrate Resistant Prostate Cancer
• Brief Summary: This is a Phase I, non-randomized, multiple-dose, 3+3 dose-escalation study of the safety, pharmacokinetics, biomarkers, preliminary efficacy and patient-reported outcomes of therapeutic vaccine, BPX-101 (formerly BP-GMAX-CD1), plus activating agent, AP1903, in patients with castrate resistant prostate cancer.
• Detailed Description: Patients will be screened within 6 weeks prior to Week 1. A total of 3 cohorts, consisting of 3 to 6 patients each, are planned to receive five to eight intradermal (ID) injections totaling 1 mL up to 1.6mL of BPX-101 at 3 doses levels for an initial 6 doses.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Castrate Resistant Prostate Cancer (CRPC)

Intervention

• Biological: BPX-101
  Vaccine
  Other Name: N/Ap
• Drug: AP1903
  Activating agent, infusion
  Other Name: N/Ap

Study Arms

Experimental: Dose escalation

Cohort 1: BPX-101, 4 x 10*6 cells administered every other week for 6 cycles Cohort 2: BPX-101, 12.5 x 10*6 cells administered every other week for 6 cycles Cohort 3: BPX-101, 25 x 10*6 cells administered every other week for 6 cycles Cohort 4: BPX-101, 25 x 10*6 cells administered every 4 weeks for 3 cycles

At 24 hours after each vaccination, a single dose of the activating agent, AP1903 for Injection, will be administered at a fixed dose of 0.4 mg/kg via intravenous (IV) infusion over 2 hours.

Interventions:

• Biological: BPX-101
• Drug: AP1903

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2009): 18
• Original Estimated Enrollment (submitted: March 24, 2009): 24
• Actual Study Completion Date: March 2012
• Actual Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Males ≥ 18 years of age
2. Histological diagnosis of adenocarcinoma of the prostate
3. Documented evidence of distant metastasis of disease
4. No more than 1 prior chemotherapeutic, biologic or combination treatment regimen (including vitamin D analogues) for CRPC. If previously treated, patients must be recovered from all toxicities prior to entry into the study.
5. Patients must have current or historical evidence of disease progression concomitant with surgical (orchiectomy) or medical castration (LHRH analogue); anti-androgen withdrawal (4 weeks for flutamide and 6 weeks for nilutamide or bicalutamide) is necessary only for patients on antiandrogens and a duration of response to antiandrogens > 3months;
6. Testosterone < 50 ng/dL achieved via medical or surgical castration. Patients receiving medical castration therapy must continue such therapy throughout the study.
7. Adequate hematologic, renal and liver function:
8. Negative serology tests for human immunodeficiency virus (HIV-1 and 2), human T-cell lymphotropic virus (HTLV-1), hepatitis B surface antigen (HBsAg) and hepatitis C (HCV)
9. Karnofsky Performance Score (KPS) ≥ 70%
10. Life expectancy > 6 months
11. Written informed consent obtained prior to the initiation of study procedures

Exclusion Criteria:

1. The presence of brain metastases, pleural effusions or ascites
2. Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography > 50%), or spinal cord compression
3. A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the patient must be disease-free at the time of registration. Patients with a history of stage I or II other cancers must have been adequately treated and been disease-free for 3 years at the time of registration.
4. More than 1 prior chemotherapy, biologic or combination treatment regimen (including vitamin D analogues) for CRPC
5. Any treatment with radiopharmaceuticals, e.g. Strontium-89 and Samarium-153
6. Ketoconazole or antiandrogens (flutamide, nilutamide, bicalutamide) within 2 weeks prior to registration. Patients who demonstrate an anti-androgen withdrawal response, defined as a > 25% drop in PSA within 4 weeks (flutamide) or 6 weeks (nilutamide, bicalutamide) of stopping a non-steroidal anti-androgen, are not eligible until the PSA rises above the nadir observed after anti-androgen withdrawal.
7. Initiation of bisphosphonate therapy within 28 days prior to registration. Patients taking bisphosphonates should not have their dosing regimen altered unless medically warranted.
8. A requirement for systemic steroid or other immunosuppressive therapy for any reason.
9. Treatment with any of the following medications or interventions < 28 days prior to Screening
10. Treatment with any investigational vaccine within 2 years prior to Screening, or treatment with any other investigational product within 28 days prior to Screening
11. Any antibiotic therapy or infection within 1 week prior to Screening, including unexplained fever (temperature ≥ 100.5F or 38.1C)
12. History of autoimmune disease
13. Serious ongoing chronic or acute illness
14. Any medical intervention or other condition which, in the opinion of the Principal Investigator and/or the Bellicum Medical Monitor, could compromise adherence with study requirements

Other Criteria Apply however are not listed

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00868595
• Other Study ID Numbers: BP-PC-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bellicum Pharmaceuticals
• Original Responsible Party: Kevin Slawin, M.D. , Sponsor Representative, Bellicum Pharmaceuticals, Inc.
• Current Study Sponsor: Bellicum Pharmaceuticals
• Original Study Sponsor: Same as current

Collaborators

• M.D. Anderson Cancer Center
• The University of Texas Health Science Center, Houston
• Memorial Hermann Hospital
• Baylor College of Medicine

Investigators

• Principal Investigator: Guru Sonpavde, MD; University of Texas Health Science Center Houston - CCTS

• PRS Account: Bellicum Pharmaceuticals
• Verification Date: October 2019