B-Cell Chronic Lymphocytic Leukemia
Conditions
Keywords
CLL, CNF2024, Hsp90 inhibitor
Brief summary
CLL dosing escalating study; daily dosing schedule; PK/PD safety
Detailed description
Phase 1, open-label, accelerated-titration study designed to evaluate the effects of increasing doses of CNF2024 on safety, pharmacokinetics, pharmacodynamic markers, and hematological response
Interventions
DRUGCNF2024 (BIIB021)
Dose starting at 12.5 mg/d, p.o. as a once-daily dose for 21 days followed by a 1-week rest period. Dose escalation will proceed according to the predetermined scheme until the maximum tolerated dose (MTD) is reached due to dose limiting toxicities (DLT) during the first course of treatment.
Sponsors
Biogen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with CLL who relapsed following or are intolerant to purine analog -based therapy * Hemoglobin \>=9 gm/dL (may be post-transfusion) * Total bilirubin \<2 X ULN, and ALT and AST \<2 x ULN * Creatinine \<=2 X ULN * Normal plasma cortisol and ACTH concentrations * ECOG Performance Status \<=2 * Anticipated survival \>=3 months * For men and women of child-producing potential, use of effective contraceptive methods during the study and for one month after treatment * Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments
Exclusion criteria
* Pregnant or nursing women * Treatment with chemotherapy, monoclonal antibody, or radiotherapy within 28 days before entering the study * Participation in any investigational drug study within 28 days before CNF2024 administration * Patients with secondary malignancy requiring active treatment (except hormonal therapy) * Active symptomatic bacterial, fungal, or viral infection including active HIV or viral (A, B, or C) hepatitis * Problems with swallowing or malabsorption * Diarrhea (excess of 2-3 stools/day above normal frequency in the past month) * Gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis * Major surgery of the stomach or small intestine * Adrenal dysfunction * Patients with life- or function-threatening CLL complications (e.g., cord compression, hemolytic crisis, urinary tract obstruction) * Any illness or condition that in the opinion of the investigator may affect safety of treatment or evaluation of any the study's endpoints
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and toxicity (maximum tolerated dose (MTD)) | 4 week periods until MTD is reached |
| Pharmacokinetics | Dosing period |
| Pharmacodynamics | Dosing period |
Secondary
| Measure | Time frame |
|---|---|
| To determine clinical and hematological response | Study Duration |
| To determine the recommended Phase 2 dose | Study duration |
Countries
United States
Outcome results
None listed