Leukemia Lymphocytic Chronic B-Cell
Conditions
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Brief summary
This is a dose finding study using a 3 + 3 dose escalation and expansion design to determine a Not Tolerated Dose (NTD), Optimal Biological Effect Dose (OBE) and / or Maximum Tolerated Dose (MTD). These data will be used to establish a Recommended Phase 2 Dose (RP2D) for the combination of CC-292 and Rituximab in subjects with CLL.
Detailed description
This dose finding study uses a 3 + 3 dose escalation and expansion design to establish the recommended Phase 2 dose (RP2D). Treatment will consist 28 day treatment cycles with a single Rituximab infusion per cycle for 6 cycles and twice daily (days 1-28) administration of CC-292 with a starting dose cohort of 375mg twice a day. Following safety review of the data from the initial cohort and confirmation that the initial dose is tolerable, the next dose level will be enrolled with a once per cycle Rituximab infusion for 6 cycles and twice daily CC-292 at 500 mg. Determination of the maximum tolerated dose and/or optimal biologic effect will be used to establish a dose for evaluation in an expansion cohort of 24 subjects. Evaluation of the data for subjects in the expansion cohorts will result in establishment of a RP2D.
Interventions
DRUGCC-292
Cohort 1: 375 mg CC-292 will be administered twice a day on Days 1-28 Cohort 2: 500 mg CC-292 will be administered twice a day on Days 1-28
DRUGRituximab
Cohort 1: Rituximab once per cycle Cohort 2: Rituximab once per cycle
Sponsors
Celgene Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects 18 years of age and older at the time of signing the informed consent document. 2. Understand and voluntarily sign an informed consent document (ICD) prior to any study related assessments/procedures being conducted. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Body weight ≥ 50 kg. 5. Must have a documented diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (International Workshop) guidelines for the diagnosis and treatment of CLL (Appendix A), or lymphoma guidelines (Appendix B) for diagnosis and treatment of SLL by investigator assessment. 6. Have failed ≥ 1 previous treatments for CLL/SLL, and have relapsed or refractory disease following last prior treatment. 1. Refractory is defined as CLL/SLL that does not achieve at least a partial response (PR) to therapy or that progresses within 6 months of treatment. Relapsed CLL/SLL refers to disease that progresses after ≥ 6 months in subjects who had achieved a PR or complete response (CR) to therapy. 2. Subjects must have failed, refused, be ineligible, or not otherwise appropriate, per the investigator's judgment, for autologous stem cell transplant (SCT) unless enrollment in this study is anticipated to debulk lesions in preparation for SCT. 7. Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤ 2 8. Life expectancy of at least 3 months form the time of signing the ICD. 9. Females of childbearing potential (FCBP)must have a negative medically supervised pregnancy test prior to starting of study therapy. 10. Male subjects must: 1. Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug treatment, during any dose interruption and for 28 days after end of study therapy. 2. Agree to not donate semen during study drug treatment and for 28 days after end of study drug treatment. 11. Ability to swallow oral capsules without difficulty. 12. Have an echocardiogram or multigated acquisition scan of the heart demonstrating left ventricular ejection fraction (LVEF) ≥ 50% or the institution's lower limit of normal. 13. Have recovered from adverse, toxic effects of prior therapies to Grade ≤ 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI/CTCAE) version 4.03 except for alopecia and peripheral neuropathy. This requirement will be subordinate to specific clinical and laboratory criteria that are otherwise specifically addressed in these inclusion/
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Up to a year | Number of participants with adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK-Tmax | Up to 15 days | Time to maximum observed plasma concentration of CC-292 in combination with Rituximab. |
| PK-λz | Up to 15 days | Terminal phase rate constant. |
| PK-t1/2 | Up to 15 days | Estimate of the terminal phase half-life in plasma. |
| PK-Cmax | Up to 15 days | Maximum observed plasma concentration |
| PK-AUC0-∞ | Up to 15 days | Area under the plasma concentration time curve from time zero extrapolated to infinity. |
| Efficacy | Up to 2 years | To evaluate the preliminary efficacy of CC-292 in combination with Rituximab, including Response Rate, Duration of Response and Progression-Free Survival |
| PK-AUC (0-t) | Up to 15 days | Area under the plasma concentration-time curve from time zero to the last quantifiable time point. |
Countries
Germany, United States
Outcome results
None listed