Oral Histone Deacetylase Inhibitor 4SC-202 in Patients With Advanced Hematologic Malignancies (TOPAS)

March 31, 2015 updated by: 4SC AG

Open Label, Dose Escalation Study of 4SC-202 in Patients With Advanced Hematologic Malignancies: First-In-Man Study of a Newly Developed, Oral Histone Deacetylase Inhibitor

The purpose of this study is to determine the Maximum Tolerated Dose, Dose Limiting Toxicities and optimal dosing schedule of 4SC-202 investigating its safety, tolerability and pharmacokinetics.

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 (Anticipated)

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.
36

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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Köln, Germany
        • Universiätsklinikum Köln
      • Stuttgart, Germany
        • Robert-Bosch-Krankenhaus
      • Würzburg, Germany
        • Universitatsklinikum Wurzburg

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:

  • Male or female patients, age ≥ 18 years.
  • Patients with Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM),Myelodysplastic Syndrome (MDS) or malignant lymphoma which are relapsed and/or refractory to standard therapy or for which no standard therapy exists. Patients who are not eligible for curative stem cell transplantation or patients who have refused or are not eligible for frontline (chemo-) therapy may also be included.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  • Patients must have a live expectancy of 12 weeks or more.
  • Patients must have adequate bone marrow reserve as well as adequate renal and hepatic function and serum electrolytes within a clinically acceptable range.
  • Patients must have recovered from any treatment-related toxicities (to Grade 0 or 1 according to Common Terminology Criteria for Adverse Events (CTCAE); except for alopecia, fatigue and Grade 1 neurotoxicity) prior to registration.

Exclusion Criteria:

  • Patients who have received previous treatment with an HDAC inhibitor.
  • Patients with any gastrointestinal disorder that could interfere with the absorption of 4SC-202
  • Patients who are unable to take oral medication.
  • Patients with a history of other malignancies unless having undergone definitive treatment more than 5 years prior to entry into the study and without evidence of recurrent malignant disease, excluding patients with basal cell carcinoma of the skin; superficial carcinoma of the bladder; carcinoma of the prostate with a current prostate specific antigen (PSA) value of < 0.1 ng/ml; or cervical intraepithelial neoplasia.
  • Patients with a history of, who were treated for, or who are suspected of having, hepatitis B, hepatitis C or human immunodeficiency virus (HIV). Patients suspected of having any of these conditions should undergo appropriate evaluations prior to being enrolled in the study.
  • Patients with precedent anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the last two weeks or a longer period depending on the known PK characteristics of the agents used.
  • Patients with history or current evidence of clinically relevant allergies or idiosyncrasy to drugs (especially of similar chemical composition to the study drug) or food.
  • Patients with symptomatic brain metastases/central nervous system (CNS) involvement.
  • Patients with significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure (New York Heart Association (NYHA) Class III or IV) related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the trial entry.
  • Patients with a marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval > 450 msec (Grade 1 CTCAE); Long-QT-Syndrome; the required use of concomitant medication on 4SC-202 dosing days that may cause Torsade de Pointes.
  • Therapy with agents known to prolong the QT interval, such as certain antibiotics (i.e. erythromycin, clarithromycin), antidepressants (i.e. doxepin, amitryptilin) or neuroleptics (i.e. haloperidol, clozapin).

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
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

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
Measure Description
Time Frame
Determination of Dose Limiting Toxicities of 4SC-202
Time Frame: 6 weeks
6 weeks
Determination of Safety of 4SC-202
Time Frame: 6 weeks
The safety and tolerability will be determined by occurrence of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
6 weeks
Determination of Pharmacokinetic Profile of 4SC-202
Time Frame: 3 weeks

The plasma concentrations of 4SC-202 will be determined at the following time-points:

Cycle 1 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 1 Day 5: Pre-dose, 0.5 h, 1h, 2h Cycle 1 Day 14: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. Cycle 2 Day 1: Pre-dose, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 8 h, 24 h p.a. using AUC0-infinity, AUClast, Cmax, tmax, t1/2, CL/F
3 weeks
Determination of Maximum Tolerated Dose of 4SC-202
Time Frame: 6 weeks
6 weeks
Determination of Tolerability of 4SC-202
Time Frame: 6 weeks
The safety and tolerability will be determined by occurrence of adverse events (AEs), vital signs (VS) [body temperature, weight, blood pressure (BP), pulse rate], electrocardiogram (ECG), performance status and clinical laboratory parameters.
6 weeks

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
Assessment of potential anticancer activity of 4SC-202
Time Frame: 6 weeks
The assessment will be performed by assessment of tumor response, duration of response and progression free survival
6 weeks
Histone deacetylase (HADAC) inhibition in peripheral mononuclear cells
Time Frame: 6 weeks
6 weeks
Histone acetylation in peripheral mononuclear cells
Time Frame: 6 weeks
6 weeks
Gene expression analysis in peripheral blood
Time Frame: 6 weeks
6 weeks
Cytokine and miRNA levels in plasma
Time Frame: 6 weeks
6 weeks

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.
4SC AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andreas Engert, Prof. MD, Universitatsklinikum Koln

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.
March 1, 2011

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.
March 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2015

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).
April 12, 2011

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.
April 28, 2011

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.
April 29, 2011

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.
April 1, 2015

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.
March 31, 2015

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.
January 1, 2014

More Information

Terms related to this study

Keywords

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.
  • 4SC-202-1-2010

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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