Dose Escalation Study to Evaluate Safety and Tolerability of an Allogeneic Tumor Vaccine BIWB 2 in Patients With Advanced Malignant Melanoma

July 30, 2014 updated by: Boehringer Ingelheim

An Open-label, Multicenter, Controlled, Combined Parallel Group and Dose Escalation (0, 0.12, 1.2, 12.0 µg IL-2/10**8 Cells/24 Hours) Study, to Evaluate the Safety and Tolerability of an Allogeneic Tumor Vaccine BIWB 2 Containing Melanoma Cells Transfected With the Human IL-2 Gene in Patients With Advanced Malignant Melanoma

Evaluation of safety and tolerability of four intradermal injections given at two week intervals. In addition the efficacy of transferrinfection was determined by quantifying Interleukin 2 (IL-2), which was locally produced by the implanted, transfected allogenic melanoma cells at the injection sites. Further determination of tumor specific and clinical host responses induced or augmented by the treatment were determined.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients who fail to respond to conventional therapy or for whom conventional therapy is not available
  • Metastatic melanoma (stage IV AJCC) which is surgically or medically incurable because of distant metastatic disease (i.e., a metastasis not in the same lymph node draining area as the primary malignant melanoma). Histologic confirmation of stage IV is required. Measurable disease that can be routinely assessed by physical examination and/or non-invasive radiological procedures
  • Karnofsky performance status is at least 60% and life expectancy greater than 4 months
  • Male or female, minimum age 18 years
  • Written informed consent of the patient in accordance with good clinical practice and local legislation
  • Availability of material for autologous Delayed Type Hypersensitivity (DTH) testing (material derived from autologous melanoma metastases and in-house preparation successful) is a requisite for entering the study
  • Patients have to undergo biopsy of at least one metastasis before the first and after the last vaccination

Exclusion Criteria:

  • Patient who have received any chemotherapy, corticosteroids, radiotherapy (stereotactic irradiation permitted), immunotherapy (e.g. Granulocyte Macrophage Colony Stimulating Factor, Granulocyte Colony Stimulating Factor) or any other investigational drugs in the 4 weeks prior to the first vaccination or prior to surgical removal of tumor specimens for DTH material preparation (patients are not permitted to receive such therapies 4 weeks prior to first cell inoculation except of tumor reductive surgery which are medically indicated)
  • Patients with active intracranial metastases (CT/MRI) or choroidal melanoma
  • Patients with active autoimmune disease
  • Patients with organ allografts
  • Patients with evidence of one or more of the following infections: HIV-1, HIV-2, Hepatitis B Virus, Hepatitis C Virus, Human T lymphotropic Virus-1
  • Patients with active systemic infections or other major medical illness of the cardiovascular organ system [e.g. coronary heart disease (New York Heart Association class III or IV), history of clinically significant ventricular arrhythmias or angina], coagulation disorder, respiratory or nervous system disorder or with severe endocrinological disease
  • Women of childbearing potential with a positive pregnancy test or without appropriate contraception (e.g. IUD [ Intra-Uterine Device], oral contraceptives) until at least 28 days after the last vaccination
  • Lactating women
  • Impaired renal or hepatic function (serum creatinine > 1.5 mg/dl or creatinine clearance < 75 ml/min). In amendments 1 and 3 serum creatinine levels were changed to 2.5 mg/dl and creatinine clearance was reduced to 30 ml/min

  • Impaired hematologic function with:

    • White Blood Count (WBC) < 2500/mm**3 or
    • absolute lymphocyte count < 1500/mm**3 or
    • hemoglobin < 8 g/dl or
    • platelets < 100,000/mm**3
  • Evidence for the existence or history of other malignant neoplasms (except adequately treated basal cell carcinoma and carcinoma in situ of the cervix)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BIBW2 with IL-2 secreting cell line
Biological: BIBW2 component B
BIBW2 with IL-2 secreting cell line
Experimental: BIBW2 without IL-2 secreting cell line
Biological: BIBW2 component A
BIBW2 without IL-2 secreting cell line

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Occurrence of dose limiting toxicity (DLT)
Time Frame: up to 6 weeks
up to 6 weeks
Number of patients with adverse events
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Grading of local reactions on a 4-point-scale
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination
Number of patients with IL-2 transcripts in biopsies of injection sites
Time Frame: 4-6 and 48 hours after first vaccination
4-6 and 48 hours after first vaccination
Number of patients with delayed type hypersensitivity skin reaction
Time Frame: up to 28 days after the last vaccination
delayed type hypersensitivity testing
up to 28 days after the last vaccination
Number of antigen-positive cells in biopsies from metastatic lesions
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination
Number of antigen-positive cells in the cellular infiltrate at the vaccination site
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination
Number of patients with a positive reaction to Multitest Merieux
Time Frame: up to day 14
positive reaction: sum of all indurations of all existing reactions => 10 mm (male) or >= 5 mm (female)
up to day 14
Change in T cell proliferation as ratio of post-vaccination to pre-vaccination
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination
Change in S-100 beta protein level in serum
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination
Number of patients with clinical response
Time Frame: up to 28 days after the last vaccination
clinical response = complete and partial response
up to 28 days after the last vaccination
Change in interferon-gamma secretion as ratio of post-vaccination to pre-vaccination
Time Frame: up to 28 days after the last vaccination
up to 28 days after the last vaccination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 1998

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2001

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 29, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 31, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1155.2

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