NFKB2 Rearrangement in Guiding Treatment with Ixazomib Citrate and Dexamethasone or Ixazomib Citrate, Dexamethasone and Lenalidomide in Patients with Relapsed or Refractory Multiple Myeloma

Active:	No
Cancer Type:	Multiple Myeloma	NCT ID:	NCT02765854
Trial Phases:	Phase II	Protocol IDs:	MMRC060 (primary) NCI-2016-00043 IRB00077815
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Emory University Hospital/Winship Cancer Institute
NCI Full Details:	http://clinicaltrials.gov/show/NCT02765854

Summary

This randomized phase II trial studies how well ixazomib citrate and dexamethasone or ixazomib citrate, dexamethasone, and lenalidomide work based on the expression 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 (recurrent) or does not respond to treatment (refractory). Ixazomib citrate 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 citrate and dexamethasone, or ixazomib citrate, dexamethasone, and lenalidomide are more effective in treating multiple myeloma.

Objectives

PRIMARY OBJECTIVES:
I. 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 3 comparisons:
Ia. 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.
Ib. 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.
Ic. 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 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 citrate 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 citrate and dexamethasone as in arm A.

ARM C (MUTATED NFKB2 REARRANGEMENT): Patients receive ixazomib citrate 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.

Treatment Sites in Georgia

Gordon Hospital
1035 Red Bud Road
Calhoun, GA 30701
706-879-5852
www.gordonhospital.com

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
404-778-5180
winshipcancer.emory.edu

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