Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT02339922|
Recruitment Status : Recruiting
First Posted : January 16, 2015
Last Update Posted : February 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lymphocytic Leukemia Follicular Lymphoma Lymphoplasmacytic Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Small Lymphocytic Lymphoma Waldenstrom Macroglobulinemia||Drug: Ixazomib Citrate Other: Laboratory Biomarker Analysis Biological: Rituximab||Phase 2|
I. To assess the efficacy of ixazomib (ixazomib citrate) as monotherapy in untreated indolent B-cell non-Hodgkin lymphoma (B-NHL) based on overall response rate.
I. To evaluate efficacy parameters including the duration of response (DOR), progression-free survival (PFS), time to next therapy (TNT), and complete response rate (CR) of ixazomib in untreated indolent B-NHL.\
II. To evaluate the safety and tolerability of ixazomib in subjects with B-NHL.
III. To evaluate the safety and tolerability of ixazomib plus rituximab in subjects with B-NHL.
IV. To evaluate the efficacy parameters including overall response rate (ORR), DOR, TNT, PFS, and CR of the combination of rituximab with ixazomib.
I. To evaluate clinical and biological prognostic and predictive biomarkers relative to treatment outcomes of ixazomib in indolent B-NHL.
Patients receive ixazomib citrate orally (PO) once weekly every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Upon completion of 6 courses of ixazomib citrate therapy, patients also receive rituximab intravenously (IV) once weekly. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Window Study of Ixazomib in Untreated Indolent B-NHL|
|Actual Study Start Date :||May 18, 2016|
|Estimated Primary Completion Date :||December 30, 2021|
Experimental: Treatment (ixazomib citrate, rituximab)
Patients receive ixazomib citrate PO once weekly every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity. Upon completion of 6 courses of ixazomib citrate therapy, patients also receive rituximab IV once weekly. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Drug: Ixazomib Citrate
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Rituximab
- ORR (CR + very good PR + PR + minor response) in patients with Waldenstrom macroglobulinemia (WM)/ lymphoplasmacytic lymphoma (LPL) [ Time Frame: Up to 5 years ]ORR will be calculated for all treated patients for each disease cohort. The corresponding 95% two-sided confidence interval will be derived.
- Overall response rate (ORR) (complete response [CR] + partial response [PR]) in patients with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), follicular lymphoma (FL), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL) [ Time Frame: Up to 5 years ]ORR will be calculated for all treated patients for each disease cohort. The corresponding 95% two-sided confidence interval will be derived.
- CR rate [ Time Frame: Up to 5 years ]
- Duration of response (DOR) [ Time Frame: From the time by which the measurement criteria are met for CR or PR, whichever is recorded first, until death or the first date by which recurrent or progressive disease is objectively documented, assessed up to 5 years ]DOR will be calculated to determine durability. Non-responders will be excluded from the analysis of DOR. Kaplan Meier methodology will be used to estimate event-free curves.
- Incidence of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after administration of the last dose of ixazomib citrate ]Safety summaries will include tabulations in the form of tables. The frequency of treatment-emergent AE's will be summarized. Additional AE summaries will include AE frequency by AE severity and relationship to the study drug. AE's requiring discontinuation of the study drug will be summarized separately, both overall and by AE severity and by relationship to the study drug. Clinically significant abnormal laboratory values will be summarized over study visits.
- Overall survival [ Time Frame: Up to 5 years ]
- Progression-free survival (PFS) [ Time Frame: Time from the first study drug administration to the first occurrence of lymphoma progression or death from any cause, assessed up to 5 years ]Data for subjects without disease progression or death will be censored at the date of the last tumor assessment. Kaplan-Meier methodology will be used to estimate the event-free curves.
- Time to next therapy (TNT) [ Time Frame: From the time of first study drug administration until the date of subsequent the first subsequent therapy given to treat the B-NHL, assessed up to 5 years ]Data for subjects that have not received additional anti-neoplastic therapy will be censored at the date of last known contact.
- Gene expression profiling on tumor specimens [ Time Frame: Up to 5 years ]Will be correlated with response to rituximab.
- Identification of clinical features (i.e. Mantle Cell International Prognostic score, Follicular Lymphoma International Prognostic Index score, and International Prognostic Scoring System score) and biomarker expression levels [ Time Frame: Up to 5 years ]
- Single nucleotide profile (SNP) genotyping for PSMB1 P11A [ Time Frame: Up to 5 years ]SNP genotyping for PSMB1 P11A will be performed and will be correlated with response to ixazomib citrate and ixazomib citrate plus rituximab.
- Tumor expression of cluster of differentiation 68, nuclear transcription factor kappa-B, p65, p27, and proteasome subunit, alpha-type, 5 by immunohistochemistry [ Time Frame: Up to 5 years ]Will be correlated with response to ixazomib citrate and ixazomib citrate plus rituximab.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339922
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Ajay K. Gopal 206-606-2037 email@example.com|
|Principal Investigator: Ajay K. Gopal|
|Principal Investigator:||Ajay Gopal||Fred Hutch/University of Washington Cancer Consortium|