Autologous Dendritic Cell-Tumor Cell Immunotherapy for Advanced Epithelial Ovarian Carcinomas

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2014 by NeoStem, Inc.
Sponsor:
Information provided by (Responsible Party):
NeoStem, Inc.
ClinicalTrials.gov Identifier:
NCT02033616
First received: January 7, 2014
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This is a double-blind study in which approximately 99 study patients will be randomized in a 2:1 ratio to receive either ovapuldencel-T (autologous dendritic cells loaded with irradiated autologous tumor cells in GM-CSF) or MC (autologous PBMC in GM-CSF). Patients eligible for treatment will be those (1) who have undergone debulking surgery, (2) for whom a cell line has been established, (3) who have undergone leukapheresis, (4) are scheduled for primary adjuvant chemotherapy, and (5) have an ECOG performance grade of 0 or 1.

The primary endpoint of this trial is death from any cause with the metric of overall survival (OS) from the date of randomization. Progression-free survival (PFS) will be a secondary endpoint and will be calculated as the time from the date of randomization for treatment until subjective tumor progression or death. Progression will be subjectively defined by the treating physician, and is expected to be based on tumor marker levels (e.g. CA-125) and/or imaging. Secondarily, we will also define PFS and OS from the date of debulking surgery.

Patients will be stratified into (1) platinum-resistant, based on progression during adjuvant chemotherapy or detectable disease at the conclusion of adjuvant therapy or (2) platinum-sensitive, with no evidence of disease (NED) at the conclusion of adjuvant therapy (per elevated blood CA-125 and/or tumor markers and/or detection of disease by physical examination or imaging).

Summary of Stratification and Treatment Plan Platinum Sensitive Platinum Resistant Ovapuldencel-T Arm Ovapuldencel-T + Paclitaxel Ovapuldencel-T+ Secondary Adjuvant therapy MC Arm Mononuclear cells + Paclitaxel Mononuclear cells + Secondary Adjuvant therapy


Condition Intervention Phase
Stage III Ovarian Carcinoma
Stage IV Ovarian Carcinoma
Fallopian Tube Carcinoma
Primary Peritoneal Carcinoma
Biological: ovapuldencel-T
Biological: MC: Autologous PBMCs in GM-CSF
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase II, Double-Blind, Randomized, Single Center Trial Of Ovapuldencel-T (Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells In GM-CSF) vs. Autologous Peripheral Blood Mononuclear Cells In GM-CSF (MC) as a Component of Maintenance or Secondary Therapy in Patients With Stage III or IV Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma After Debulking Surgery and Adjuvant Chemotherapy

Resource links provided by NLM:


Further study details as provided by NeoStem, Inc.:

Primary Outcome Measures:
  • Primary Efficacy Endpoint: Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Overall Survival: time to death from date of randomization


Secondary Outcome Measures:
  • Secondary Efficacy Endpoints: Success rate for establishing a tumor cell line [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Secondary Efficacy Endpoints: The success rate for establishing patient tumor cell lines

  • Secondary Efficacy Endpoint: Progression Free Survival (PFS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Progression Free Survival: time to disease progression or death from date of randomization

  • Secondary Efficacy Endpoint: OS and PFS for platinum-sensitive patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Secondary Efficacy Endpoint: OS and PFS for the subset of patients who are platinum-sensitive and have no evidence of disease (NED) after adjuvant therapy

  • Secondary Efficacy Endpoint: OS and PFS for platinum-resistant patients [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Secondary Efficacy Endpoint: OS and PFS for the subset of patients who are platinum-resistant after/during primary adjuvant chemotherapy

  • Secondary Efficacy Endpoints: OS and PFS from date of debulking surgery and diagnosis [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Secondary Efficacy Endpoints: OS and PFS from date of debulking surgery and date of diagnosis


Other Outcome Measures:
  • Safety Endpoints: Adverse events attributed to ASI therapy [ Time Frame: Within 30 days from administration ] [ Designated as safety issue: Yes ]
    Safety Endpoints: Adverse events attributed to the vaccine therapy (including GM-CSF) and not attributed to chemotherapy to assess safety and tolerability

  • Safety Endpoint: Abnormal findings attributed to the ASI therapy [ Time Frame: Within 30 days from administration ] [ Designated as safety issue: Yes ]
    Safety Endpoint: Abnormal findings by history & physical examination, vital signs, clinical laboratory tests (safety), and other tests as clinically indicated that might be attributed to the ASI therapy


Estimated Enrollment: 99
Study Start Date: January 2015
Estimated Study Completion Date: December 2022
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ovapuldencel-T
ovapuldencel-T (autologous dendritic cells loaded with antigens from irradiated autologous tumor cells and suspended in GM-CSF): 5-10 million cells given over 6 months via SC injection, concurrent with maintenance or secondary chemotherapy
Biological: ovapuldencel-T
Comparison of a cancer treatment containing autologous irradiated tumor cells mixed with autologous antigen presenting immune cells suspended in an immune system stimulant vs. a cancer treatment containing autologous immune cells suspended in an immune system stimulant.
Active Comparator: MC: Autologous PBMCs in GM-CSF
MC (autologous peripheral blood mononuclear cells suspended in GM-CSF will serve as the control arm): taken over 6 months via SC injection concurrent with maintenance or secondary chemotherapy
Biological: MC: Autologous PBMCs in GM-CSF
Comparison of a cancer treatment containing autologous irradiated tumor cells mixed with autologous antigen presenting immune cells suspended in an immune system stimulant vs. a cancer treatment containing autologous immune cells suspended in an immune system stimulant.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Pre-Treatment Phase: Tissue Procurement and Establishment of Tumor Cell Line

  • Histologic diagnosis of epithelial ovarian, fallopian tube or primary peritoneal carcinoma.
  • Advanced (metastatic, stage III or IV) epithelial ovarian, fallopian tube or primary peritoneal carcinoma and a candidate for surgical debulking to obtain fresh viable tumor tissue for efforts to establish a short-term tumor cell line.
  • Age > 18 years
  • Each patient must be aware of the neoplastic nature of her disease process and must willingly consent to the manipulation of tumor tissue for efforts to establish a tumor cell line. Patients will sign a Tissue Informed Consent to allow their tissue to be given to California Stem Cell, Inc., and for efforts to establish an autologous tumor cell line
  • Patients must have the ability and willingness to travel to Newport Beach, California for administration of ASI treatment.

Treatment Phase

  • Successful establishment of an autologous epithelial ovarian, fallopian tube, or primary peritoneal cancer cell line by California Stem Cell, Inc.
  • Patients must previously have been staged as having stage III (intraperitoneal) or Stage IV (distant metastatic) ovarian, fallopian tube, or primary peritoneal cancer, have undergone surgical debulking, and have initiated or completed standard adjuvant chemotherapy, which may include intravenous and/or intraperitoneal chemotherapy using standard regimens. Patients will be characterized as being in complete remission per physical exam, CT scans, and CA-125, or not in complete remission.
  • Medical fitness to undergo a leukapheresis, including peripheral venous access or access by central vein if necessary.
  • Negative pregnancy test for women of childbearing potential and use of effective contraception (hormonal or barrier method of birth control) for women of childbearing potential prior to therapy, during therapy, and 4 months after completing therapy.
  • Patients with one or a few brain metastases that have been treated with stereotactic radiotherapy consisting of a single dose, such as Gamma Knife or Cyberknife, are allowed to be included in the study, but need wait one week after such treatment..
  • Additional written informed consent for treatment with ASI including explanation of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts associated with this investigational therapy, will be obtained.

Exclusion Criteria:

Pre-Treatment Phase: Tissue Procurement and Establishment of Tumor Cell Line

• ECOG performance status greater than 2.

Treatment Phase

  • Known positive for hepatitis B or C or HIV.
  • Pregnant or lactating women.
  • Underlying cardiac disease associated with myocardial dysfunction that requires active medical treatment, or unstable angina related to atherosclerotic cardiovascular disease, or under treatment for arterial or venous peripheral vascular disease
  • Diagnosis of any other invasive cancer which is considered to be life-threatening within the next five years, and/or taking anti-cancer therapy for cancer other than ovarian (such as continuation of hormonal therapy for prostate or breast cancer diagnosed more than five years earlier).
  • Active infection or other active medical condition that could be eminently life-threatening, including active blood clotting or bleeding diathesis.
  • Active central nervous system metastases at the time of treatment.
  • Known autoimmune disease, immunodeficiency, or disease process that involves the use of immunosuppressive therapy.
  • A low malignancy potential tumor.
  • Received another investigational drug within 28 days of the first dose.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02033616

Contacts
Contact: Jim Langford 949-7251750 ext 189 jlangford@neostem.com
Contact: Candace Hsieh, PhD 949-7251750 ext 139 chsieh@neostem.com

Locations
United States, California
NeoStem Oncology Not yet recruiting
Irvine, California, United States, 92612
Contact: Jim Langford    949-725-1750 ext 189    jlangford@neostem.com   
Principal Investigator: Robert Dillman, MD         
Sponsors and Collaborators
NeoStem, Inc.
Investigators
Study Chair: Robert Dillman, MD NeoStm Oncology, LLC
  More Information

No publications provided

Responsible Party: NeoStem, Inc.
ClinicalTrials.gov Identifier: NCT02033616     History of Changes
Other Study ID Numbers: CL-OVA-P00-00-US
Study First Received: January 7, 2014
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Fallopian Tube Neoplasms
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases

ClinicalTrials.gov processed this record on September 18, 2014