Trial Design: This is a Phase 3 randomized, open-label, active-controlled, balanced, multi-site, group sequential confirmatory trial to evaluate the progression-free survival, overall response rate, and the overall survival in CLL subjects treated with dinaciclib compared to ofatumumab.
Two interim analyses will be performed in this study. The endpoint(s), timing, and purpose of each interim analysis (IA) are summarized in the Section 8.9. The decision rule and other statistical details are further described in Section 8.0 of the protocol.
An independent response adjudication committee will assess blinded data on response and disease progression using the 2008 International Workshop on CLL (iwCLL) criteria. The Sponsor project team will be blinded to adjudication committee assessments. The adjudication committee assessed response will be used for both the interim analyses and the final analysis.
Subject Inclusion Criteria
A subject must meet all the criteria listed below to participate in the trial:
1. 18 years of age or older, or either sex, and of any race
2. Confirmed diagnosis of CLL, as defined by iwCLL criteria
3. Must have fludarabine or chemoimmunotherapy refractory disease defined as follows
* Fludarabine refractory defined as failing to respond to or relapsed within 6 months of completing fludarabine or another purine analog (e.g., pentostatin) alone or in combination regimens
* Chemoimmunotherapy refractory defined as failing to respond to chemoimmunotherapy or relapsed within 24 months of completing therapy with a combination of chemotherapy plus an anti-CD20 monoclonal antibody.
4. Eastern Cooperative Oncology Group (ECOG) Performance status 0, 1, or 2
5. Adequate organ function and laboratory parameters to include:
* Creatinine <= 2.0 mg/dL
* Bilirubin <= 1.5 x ULN (unless secondary to Gilbert[Single Quote]s)
* AST and ALT <= 2 x ULN, or if CLL involvement of the liver <= 5 x ULN
* White blood cell count < 150 x 109/L
6. Women who are sexually active, including both female subjects and the female sexual partners of male subjects, of child-bearing potential must agree to use a medically accepted method of contraception prior to enrollment, while receiving protocol-specified medication, and for 6 months after stopping dinaciclib and 12 months after stopping ofatumumab. Acceptable methods of contraception include double barrier methods such as male or female condom in combination with spermicide, or diaphragm or cervical cap or medically prescribed intrauterine device with spermicide. Contraceptive medications (i.e. oral contraceptives), vasectomy, and tubal ligation should be considered a single barrier.
7. Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study.
8. To participate in the pharmacogenetic analysis, the subject must be willing to give written informed consent for the pharmacogenetic testing and able to adhere to dose and visit schedules. Note: A subject unwilling to sign the informed consent for pharmacogenetic testing may be included in the trial; however, pharmacogenetic samples must not be obtained.