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Autologous Dendritic Cell-Tumor Cell Immunotherapy for Metastatic Melanoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Caladrius Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01875653
First received: June 7, 2013
Last updated: April 25, 2016
Last verified: January 2016
  Purpose

The purpose of this research is to evaluate the safety and effectiveness of tumor cell therapy.

This research study is evaluating if a patient-specific experimental therapy for metastatic melanoma will lengthen survival with minimal harmful effects. It is called an experimental therapy (or "study therapy") because it is not yet approved by the U.S. Food and Drug Administration (FDA). This research study will use the patient's own tumor cells,the patient's own dendritic cells (a type of immune cell), and a granulocyte-macrophage colony stimulating factor (GM-CSF, a type of growth factor). GM-CSF is a natural growth factor that stimulates growth of white blood cells in the body. Since 1991, GM-CSF has been used as a standard treatment to help increase the number of white blood cells after chemotherapy.

The patient's dendritic cells are grown in a test-tube with the patient's tumor cells and the growth factor. The resulting solution is called the study therapy. The intent of the study therapy is to make the dendritic cells more effective at fighting the tumor when they are injected back into the patient.


Condition Intervention Phase
Stage IV Melanoma
Stage III Melanoma
Biological: Autologous Dendritic Cell-Tumor Cell Immunotherapy (DC-TC)
Biological: Autologous PBMCs in GM-CSF (MC)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase III, Randomized, Double-Blind, Multicenter Trial of Autologous Dendritic Cells and Irradiated Autologous Tumor Cells In Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) vs. Autologous Peripheral Blood Mononuclear Cells (PBMCs) In GM-CSF for The Treatment Of Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Caladrius Biosciences, Inc.:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 52 months ]
    The time frames are estimated time in months (rounded up to the nearest month) from the start of study. The time estimates for the analyses are based on enrolling approximately 250 patients over a 34.8 months period and having a follow up of approximately 17 months after the last patient is enrolled.


Secondary Outcome Measures:
  • Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 52 months ]
    • Adverse Events monitoring to assess safety and tolerability
    • History & physical examination, vital signs, clinical laboratory tests (safety), and other tests as clinically indicated adverse event monitoring to assess safety and toxicity


Estimated Enrollment: 250
Study Start Date: October 2014
Estimated Study Completion Date: June 2022
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Autologous PBMCs in GM-CSF (MC)

DOSE/ROUTE/REGIMEN:

  1. Treatment Duration: Doses of MC will be administered subcutaneously weekly for 3 consecutive weeks, then monthly for the next 5 months.
  2. Dosage: Each dose of MC contains approximately 10 million cells. Each dose is suspended in 500 mcg GM-CSF prior to administration.
  3. Mode of Administration: Subcutaneous (SC) injections.
Biological: Autologous PBMCs in GM-CSF (MC)
Comparison of a cancer treatment containing patient specific irradiated tumor cells mixed with antigen presenting immune cells suspended in an immune system stimulant vs. a cancer treatment containing patient specific immune cells suspended in an immune system stimulant
Experimental: Autologous Dendritic Cell-Tumor Cell Immunotherapy (DC-TC)

DOSE/ROUTE/REGIMEN:

  1. Treatment Duration: Doses of DC-TC will be administered subcutaneously weekly for 3 consecutive weeks, then monthly for the next 5 months.
  2. Dosage: Each dose of DC-TC contains approximately 10-20 million cells. Each dose is suspended in 500 mcg GM-CSF prior to administration.
  3. Mode of Administration: Subcutaneous (SC) injections.
Biological: Autologous Dendritic Cell-Tumor Cell Immunotherapy (DC-TC)
Comparison of a cancer treatment containing patient specific irradiated tumor cells mixed with antigen presenting immune cells suspended in an immune system stimulant vs. a cancer treatment containing patient specific immune cells suspended in an immune system stimulant
Other Names:
  • DC-TC
  • MAC-VAC
  • Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells In GM-CSF
  • Melapuldencel-T

Detailed Description:
Learn more about this clinical trial at http://TheIntusStudy.com. Type or copy and paste http://TheIntusStudy.com in your browser window.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

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

  1. Histologic diagnosis of invasive melanoma.
  2. Measurable metastatic melanoma with at least one lesion amenable to -resection Stage III: recurrent regional disease, including regional disease with no known primary.

    Stage IV: distant metastatic melanoma.

  3. Age 18 years and older.
  4. Sign the "Tissue Consent", the pre-Clinical Informed Consent for Melanoma Tissue Procurement and initiation of cell line effort granting Caladrius permission to cryopreserve the tumor and/or to initiate an autologous tumor cell line from excess tissue that has been removed during a medical procedure (e.g., surgically excised).
  5. Initiation of Autologous Tumor Cell Line. Caladrius must have received a viable melanoma tumor tissue specimen that has been obtained and processed according to company SOPs to ensure tissue viability. The cell line can be initiated with either a specimen of fresh tumor or tumor that has been previously cryopreserved.

Treatment Phase

  1. Successful establishment of an autologous melanoma cell line by Caladrius.
  2. Patients with multiple depots of distant metastatic disease must have previously received at least one or more of the following standard treatments: interleukin 2 (IL-2), or ipilimumab, or vemurafenib (if tumor expresses the V600E mutation), or dacarbazine or temozolomide, if not mutated for the V600E mutation, and not felt to be medically appropriate for IL-2 or ipilimumab. These may have been given alone, or in combination with other agents.
  3. Medical fitness to undergo a leukapheresis, including peripheral venous access or access by central vein if necessary.
  4. Medical fitness for participation in a phase III clinical trial.

    • a. ECOG performance status of 0 or 1.
    • b. Adequate bone marrow function: absolute neutrophil count (ANC) greater than 1000/mm (3), hematocrit greater than 30%, platelet count greater than 100,000/mm (3), no ongoing transfusion requirements.
    • c. Adequate hepatic function: total bilirubin less than 2.0 mg/dL, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal (ULN), albumin greater than 3 g/dL.
    • d. Adequate kidney function: creatinine less than or equal to 2.0 mg/dL.
    • e. Negative pregnancy test for woman of childbearing potential and use of effective contraception (hormonal or barrier method of birth control) during therapy (women of childbearing potential and men).
  5. Extent of disease established within 4 weeks of randomization.

    • a. History and Physical Exam by a licensed practitioner.
    • b. Fludeoxyglucose(FDG)-based PET/CT or PET scan and CT scan.
    • c. Brain MRI demonstrating no new untreated or uncontrolled metastases.
  6. Recovery from previous therapies.

    • a. At least four weeks (28 days) must have elapsed since any prior systemic therapy at the time of the first dose (six weeks for anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4), and any toxicities experienced must have recovered to a grade 1 or less (except for alopecia or vitiligo).
    • b. More than three weeks (at least 22 days) since radiation therapy at the time of the first dose (7 days for single-dose stereotactic radiotherapy such as gamma knife) and recovery from acute toxicities. Patients treated with whole brain radiation must wait at least 22 days after completion of radiation and have radiographic confirmation of lack of progression before proceeding to randomization.

EXCLUSION CRITERIA:

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

  1. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2
  2. Lack of a metastatic melanoma lesion that can be resected.

Treatment Phase

  1. Known positive for hepatitis B or C or HIV.
  2. Pregnant or lactating women.
  3. Underlying cardiac disease associated with known myocardial dysfunction, or active treatment with digoxin or other medications being given to treat heart failure, or unstable angina related to atherosclerotic cardiovascular disease.
  4. Diagnosis of any other invasive cancer that requires ongoing treatment or for which there is evidence of active disease.
  5. Active, unresolved infection and/or receiving concurrent treatment with parenteral antibiotics (patients are eligible after antibiotics have been discontinued for at least 7 days prior to first dose and evidence of infection has resolved).
  6. Other active medical condition that could be imminently life threatening, in the opinion of the investigator, including no active blood clotting or bleeding diathesis.
  7. New or uncontrolled brain metastases or leptomeningeal disease and/or taking pharmacological doses of corticosteroids. Brain metastases treated by gamma knife or stereotactic radiotherapy are considered controlled, unless patient requires pharmacologic doses of corticosteroids. It is recognized that tumor necrosis may be confused with tumor progression in interpretation of Brain MRI.
  8. Known autoimmune disease, immunodeficiency, or disease process that involves the use of immunosuppressive therapy.
  9. Taking other anticancer therapy.
  10. 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: NCT01875653

Locations
United States, California
Irvine, California, United States, 92612
La Jolla, California, United States, 92093
Los Angeles, California, United States, 90033
Newport Beach, California, United States, 92625
Orange, California, United States, 92868
Santa Monica, California, United States, 90404
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Indiana
Goshen, Indiana, United States, 46526
United States, Kentucky
Louisville, Kentucky, United States, 40506
United States, Louisiana
Marrero, Louisiana, United States, 70072
United States, Maryland
Baltimore, Maryland, United States, 21237
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, Ohio
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Easton, Pennsylvania, United States, 18020
Philadelphia, Pennsylvania, United States, 19107
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Knoxville, Tennessee, United States, 37996
United States, Texas
Dallas, Texas, United States, 75251
Sponsors and Collaborators
Caladrius Biosciences, Inc.
Investigators
Study Chair: Robert O Dillman, MD Caladrius Biosciences
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Caladrius Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01875653     History of Changes
Other Study ID Numbers: CL-CA-P01
2015-001984-38 ( EudraCT Number )
Study First Received: June 7, 2013
Last Updated: April 25, 2016

Keywords provided by Caladrius Biosciences, Inc.:
metastatic melanoma
dendritic cells
immunotherapy
Granulocyte-Macrophage Colony Stimulating Factor
overall survival
autologous
peripheral blood mononuclear cells
treatment
phase 3
tumor cells

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on May 25, 2017