Ixazomib with Pomalidomide, Clarithromycin and Dexamethasone in Treating Patients with Multiple Myeloma
brief summary
This phase I/II trial studies the side effects and best dose of clarithromycin when given together with ixazomib citrate, pomalidomide, and dexamethasone and to see how well it works in treating patients with multiple myeloma that has not responded to previous treatment. Biological therapies, such as clarithromycin, pomalidomide, and dexamethasone, use substances made from living organisms that may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving clarithromycin with ixazomib citrate, pomalidomide and dexamethasone may be a better treatment for patients with multiple myeloma.
detailed description
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) for PiC-D therapy (pomalidomide, ixazomib \[ixazomib citrate\], clarithromycin, and dexamethasone) in patients with multiple myeloma who are bortezomib and lenalidomide refractory. (Phase I) II. To determine the complete response (CR) and stringent CR (sCR) rate for PiC-D therapy in patients with multiple myeloma who are bortezomib and lenalidomide refractory. (Phase II)
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of PiC-D therapy. (Phase I) II. To characterize the pharmacokinetics (PK) in plasma of oral ixazomib in combination with pomalidomide, clarithromycin and dexamethasone. (Phase I) III. To assess preliminary evidence of clinical activity. (Phase I) IV. To assess the effects of PiC-D therapy on quality of life (QOL). (Phase I) V. To assess the effects of PiC-D therapy on immune status (phenotypic analysis and cytokine profiling).
VI. To evaluate the safety of PiC-D therapy. (Phase II) VII. To determine the overall response rate (ORR) (ORR; CR, sCR, partial response, and very good partial response. (Phase II) VIII. To determine the clinical benefit rate (CBR) (CBR; minimal response + ORR). (Phase II) IX. To determine the disease control rate (DCR) (DCR; stable disease + CBR). (Phase II) X. To determine the duration of response (DOR) in patients achieving a partial response or better. (Phase II) XI. To determine the time to next treatment (TNT). (Phase II) XII. To determine progression free survival (PFS) and overall survival (OS). (Phase II) XIII. To assess the effects of PiC-D therapy on quality of life (QOL). (Phase II)
TERTIARY OBJECTIVES:
I. To assess the effects of PiC-D therapy on immune status (phenotypic analysis and cytokine profiling). (Phase II)
OUTLINE: This is a phase I, dose-escalation study of clarithromycin followed by a phase II study.
Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21; ixazomib citrate PO on days 1, 8, and 15; clarithromycin PO twice daily (BID) on days 15-21 of course 1 and days 1-21 and courses 2-6; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY:
official title
Phase I/II Study of Ixazomib in Combination with Pomalidomide, Clarithromycin and Dexamethasone (PiC-D) in Patients with Double Refractory Multiple Myeloma