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Advanced Hematologic MalignanciesPhase 1NCT01344707

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

A Phase 1 study testing 4SC-202 in people with Advanced Hematologic Malignancies, run by 4SC AG at 3 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hematologic Malignancies
What is being tested?
4SC-202
Type of treatment
Pill or oral medicine
How many people
36 participants
Where
3 sitesGermany
Study dates
Mar 2011to Mar 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

3 sites in 1 country.

Germany3 sites
  • Universiätsklinikum Köln

    Cologne

  • Robert-Bosch-Krankenhaus

    Stuttgart

  • Universitätsklinikum Würzburg

    Würzburg

Other trials in Germany

About this study

Official title: 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.

Being tested
4SC-202
Keywords
Hematologic Malignancies, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), Myelodysplastic Syndrome (MDS), Malignant Lymphomas, Histone Deacetylase (HDAC), 4SC-202, Phase I
Medical subject headings
Hematologic Neoplasms, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Multiple Myeloma, Myelodysplastic Syndromes, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 4SC-202Drug

    oral administration dose escalation twice daily (bid)or three times a day (tid) continuous dosing for 21 days per cycle

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of Dose Limiting Toxicities of 4SC-202

    Measured: 6 weeks

  2. Determination of Safety of 4SC-202

    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.

    Measured: 6 weeks

  3. Determination of Pharmacokinetic Profile of 4SC-202

    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

    Measured: 3 weeks

  4. Determination of Maximum Tolerated Dose of 4SC-202

    Measured: 6 weeks

  5. Determination of Tolerability of 4SC-202

    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.

    Measured: 6 weeks

Secondary outcomes (5)
  1. Assessment of potential anticancer activity of 4SC-202

    The assessment will be performed by assessment of tumor response, duration of response and progression free survival

    Measured: 6 weeks

  2. Histone deacetylase (HADAC) inhibition in peripheral mononuclear cells

    Measured: 6 weeks

  3. Histone acetylation in peripheral mononuclear cells

    Measured: 6 weeks

  4. Gene expression analysis in peripheral blood

    Measured: 6 weeks

  5. Cytokine and miRNA levels in plasma

    Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Apr 2011 (estimated)
  2. Study startMar 2011
  3. Primary completionMar 2015
  4. Study completionMar 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01344707
Sponsor's protocol ID
4SC-202-1-2010
Status last verified
Jan 2014
First submitted
12 Apr 2011
Last updated
1 Apr 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 4SC-202 in people with Advanced Hematologic Malignancies, run by 4SC AG at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of Dose Limiting Toxicities of 4SC-202 (time frame: 6 weeks). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2015.

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