Phase 1b/2 Study of Dinaciclib (SCH 727965) and Ofatumumab in Relapsed and Refractory CLL/SLL/B-PLL
I. To determine the tolerable dose of combination therapy with ofatumumab and dinaciclib
(phase 1b component) in chronic lymphocytic leukemia (CLL), small lymphocytic leukemia
(SLL), and B-cell prolymphocytic leukemia (B-PLL).
II. To characterize the toxicity of combination therapy with ofatumumab and dinaciclib in
III. To determine the overall response rate associated with this treatment as assessed by
consensus response criteria. (Phase II)
I. To estimate progression-free survival (PFS) after combination treatment with ofatumumab
II. To characterize the pharmacokinetics of dinaciclib when given in combination with
III. To correlate pharmacokinetic features of dinaciclib with response, toxicity
(particularly tumor lysis syndrome), and pharmacodynamic endpoints.
IV. To perform detailed baseline and serial pharmacodynamic studies of combination therapy
with ofatumumab and dinaciclib and correlate these with response to therapy.
V. To correlate baseline disease-risk parameters (i.e., ZAP-70 expression, interphase
cytogenetics, IgVH mutational analysis, and other clinical prognostic factors) with response
to therapy. (Exploratory)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive ofatumumab IV over 4-6 hours on days 1, 8, 15, and 22 of courses 1-2, and
on day 1 of courses 4-7. Beginning on course 2, patients also receive dinaciclib IV over 2
hours on days 2, 8, and 15 of course 2, and on days 1, 8, and 15 of courses 3-7. Treatment
repeats every 28 days for up to 7 courses in the absence of disease progression or
Plasma, serum, urine, and buccal swab samples are collected at baseline and periodically
during study for pharmacokinetic, pharmacogenomic, and pharmacodynamic studies, and other
After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for up to 5 years.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose graded according to the National Cancer Institute (NCI ) CTCAE v4.0 (Phase I)
Assessed using the continuous variables as the outcome measures (primarily nadir and percent change from baseline values) as well as categorization.
Up to day 56
Ohio State University Comprehensive Cancer Center
United States: Food and Drug Administration
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Columbus, Ohio 43210-1240|