NCT02765854

Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement

Phase II Trial of Ixazomib and Dexamethasone Versus Ixazomib, Dexamethasone and Lenalidomide, Randomized With NFKB2 Rearrangement. (Proteasome Inhibitor NFKB2 Rearrangement Driven Trial, PINR)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Emory University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase II trial studies how well ixazomib and dexamethasone or ixazomib, dexamethasone, and lenalidomide work based on the presence of the rearrangement of a gene called nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2) in treating patients with multiple myeloma that has returned after a period of improvement or does not respond to treatment. Ixazomib may stop the growth of cancer cells by blocking enzymes called proteasomes needed for cell growth. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lenalidomide may stimulate the immune system against cancer cells and may also prevent the growth of new blood vessels that tumors need to grow. It is not yet known whether ixazomib and dexamethasone, or ixazomib, dexamethasone, and lenalidomide are more effective in treating multiple myeloma.

Detailed description

PRIMARY OBJECTIVES: To test whether the NFKB2 rearrangement can guide the selection of treatment (ixazomib \[ixazomib citrate\] plus dexamethasone \[Id\] or ixazomib plus lenalidomide and dexamethasone \[IRd\]) by conducting the following comparisons: I. To compare the response rate at 4 cycles between patients treated with Id and patients treated with IRd and confirm the lack of significant difference in overall response. II. To compare the response rate at 4 cycles between non-rearranged and rearranged NFKB2 treated with Id and confirm that NFKB2 rearrangement is associated with reduce response rate. III. To compare the responses rate at 4 cycles of patients with rearranged NFKB2 treated with Id or IRd and confirm that adding lenalidomide increases the response rate in this population. SECONDARY OBJECTIVES: I. To determine time to treatment failure (TTF). II. To determine the frequency and severity of adverse events (AE) in IRd treated cohort. III. To identify novel transcribed mutations associated with Id and IRd resistance in patients with multiple myeloma (MM). IV. To determine the prevalence of NFKB2 rearrangement in relapsed/refractory MM patients screened in the study. V. To determine the prevalence of NFKB2 rearrangement according to the type of previous therapies received in all patients screened in the study. VI. To determine the toxicity profile of the study drugs according to the presence of NFKB2 rearrangement. VII. Delineate transcribed mutations associated with relapse or refractoriness to Id or IRd treatment by ribonucleic acid (RNA)-sequencing. OUTLINE: ARM A (UNMUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib orally (PO) on days 1, 8, and 15 and dexamethasone PO on days 1, 8, 15, and 22. Patients with mutated NFKB2 rearrangement are randomized in to 1 of 2 treatment arms. ARM B (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A. ARM C (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib and dexamethasone as in arm A and lenalidomide PO daily on days 1-21. In all arms, cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients may proceed to autologous stem cell transplant after 4 cycles of treatment. After completion of study, patients are followed up monthly.

Conditions

• Recurrent Plasma Cell Myeloma
• Refractory Plasma Cell Myeloma

Interventions

Type	Name	Description
DRUG	Dexamethasone	Given PO
DRUG	Ixazomib	Given PO
DRUG	Lenalidomide	Given PO

Timeline

• Start date: 2016-09-01
• Primary completion: 2023-05-23
• Completion: 2023-05-23
• First posted: 2016-05-09
• Last updated: 2025-06-26
• Results posted: 2025-06-26

Locations

4 sites across 1 country: United States