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
- 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
- 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.
- Patients who have received previous treatment with an HDAC inhibitor.
- Patients with any gastrointestinal disorder that could interfere with the absorption
- 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
- 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
- Patients with history or current evidence of clinically relevant allergies or
idiosyncrasy to drugs (especially of similar chemical composition to the study drug)
- 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
- 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).