Phase 1, Dose-Escalation Study of Oral CNF2024(BIIB021) in CLL

Study Overview
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Brief Summary
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CLL dosing escalating study; daily dosing schedule; PK/PD safety

Detailed Description
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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

Official Title
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A Phase 1, Dose-Escalation Study of CNF2024 Administered Orally to Patients With B Cell Chronic Lymphocytic Leukemia (CLL)

Conditions
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B-Cell Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: CNF2024 (BIIB021)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNF2024<br> | Drug: CNF2024 (BIIB021)<br>* 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.<br>* Other names: Single arm trial; no comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity (maximum tolerated dose (MTD)) |  | 4 week periods until MTD is reached | 
| Pharmacokinetics |  | Dosing period | 
| Pharmacodynamics |  | Dosing period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine clinical and hematological response |  | Study Duration | 
| To determine the recommended Phase 2 dose |  | Study duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CLL, CNF2024, Hsp90 inhibitor