Doxil, Vincristine, Decadron and Revimid (DVd-R); A Phase I/II for Relapsed/Refractory Multiple Myeloma
To identify the maximum tolerated dose (MTD) of CC-5013 [Revimid™ (R)] in combination with Doxil®, vincristine and dexamethasone (DVd) as treatment for subjects with relapsed or refractory multiple myeloma (MM).
To evaluate the overall safety of CC-5013 [Revimid™] when combined with DVd as treatment for subjects with relapsed or refractory MM.
To evaluate the preliminary efficacy of CC-5013 [Revimid™] when combined with DVd
To evaluate the effect of combination DVd-R on biological markers, coagulation parameters and myeloma paraprotein levels
This is a single-center, single-arm, open-label study of CC-5013 [Revimid™ (R)]) plus Doxil®, vincristine, and dexamethasone (DVd). The study will be a standard dose-escalation study to determine the MTD within the first 35 days of therapy with CC-5013 in combination with fixed doses of Doxil 40® mg / m2 IVPB Day 1, vincristine 2.0 mg IVP Day 1 and dexamethasone 40 mg PO daily days 1 - 4. A maximum enrollment of 40 subjects is anticipated for this study.
Maximal Tolerated Dose (MTD) Phase
Subjects will be screened within 28 days of baseline as outlined in Section 2 Schedule of Study Assessments. Subjects meeting all inclusion/exclusion criteria will be enrolled in cohorts of 3-6 to receive CC-5013 in combination with DVd in a 35-day cycle. Five dose groups are planned. For each subject in the MTD phase, Cycle 1 CC-5013 will be started on Day 1 and the initiation of DVd will be delayed until Day 8 to facilitate the drawing biological blood studies while the subject is taking only CC-5013. The resulting length of Cycle 1 is 35 days instead of 28 days.
During the MTD phase, a dose-limiting toxicity (DLT) is defined as a grade 3 or greater non-hematological toxicity or grade 4 hematological toxicity using Appendix VIII: . The study will follow a sequential dose-escalation, “3 + 3” design. Initially, three subjects will be started on treatment with dose regimen 1 as defined in Section 7.5 Treatments. After the third subject completes 35 days of treatment, if no dose-limiting toxicity occurs, then the next group of 3 subjects will be treated at the next higher dose regimen. If 1 of the 3 initial subjects experiences a DLT, the cohort of subjects will be expanded to 6 subjects. If fewer than two DLTs occur in 6 subjects, then the next higher dose group will be initiated. If 2 or more (of a cohort of up to 6) subjects experience DLT, no further dose escalations will occur and the MTD will have been exceeded. A similar approach will be followed for each dose escalation. Serial measurements of safety during the MTD phase will be performed at each visit as outlined in Section 2: Schedule of Study Assessments. Ten additional subjects will be enrolled at the MTD.
Subjects who complete the MTD phase of the study without evidence of disease progression may continue on DVd-R, until disease progression is confirmed or study drug is discontinued for any reason. During the extension phase, the subject may continue to receive a maximum of 5 additional 28-day cycles of their assigned DVd-R dose. Subjects with evidence of progression at any visit will be discontinued from the study. Subjects with at least stable disease may continue in the extension phase until “best response” is determined (Appendix II: SWOG Response Definitions). Upon the determination of “best response”, 2 additional cycles of DVd-R will be administered (a maximum of 6 cycles of DVd-R may be administered). Serial measurements of safety and efficacy during the extension phase will be performed at each visit as outlined in Section 2: Schedule of Study Assessments. Subjects will continue on DVd-R as defined above or until disease progression is confirmed or study drug, CC-5013, is discontinued for another reason.
Safety (type, frequency, severity, and relationship of adverse events to DVd-R).
Myeloma paraprotein response
Correlation of exploratory biological and coagulation studies with myeloma paraprotein response
Study drug treatment continues for a maximum of 6 cycles, until lack of therapeutic effect is documented, or study drug, C-5013, is discontinued for any reason.
Page Last Updated 09/02/2003 03:09:17 PM