Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma

NCT02339922 | Active Not Recruiting Phase 2 Results

• 4 other identifiers: 9571NCI-2016-004019224RG1716009
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ixazomib citrate and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that grows slowly (indolent). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.

Conditions

Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia; Chronic Lymphocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• 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)

  ORR will be calculated for all treated patients for each disease cohort. The corresponding 95% two-sided confidence interval will be derived.

  Up to 5 years

• ORR (CR + Very Good PR + PR + Minor Response) in Patients With Waldenstrom Macroglobulinemia (WM)/ Lymphoplasmacytic Lymphoma (LPL)

  ORR will be calculated for all treated patients for each disease cohort. The corresponding 95% two-sided confidence interval will be derived.

  Up to 5 years

Secondary Outcomes (6)

• Duration of Response (DOR)

  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

• Progression-free Survival (PFS)

  Time from the first study drug administration to the first occurrence of lymphoma progression or death from any cause, assessed up to 5 years

• Overall Survival

  Up to 5 years

• CR Rate

  Up to 5 years

• Time to Next Therapy (TNT)

  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

Other Outcomes (4)

• 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

  Up to 5 years

• Single Nucleotide Profile (SNP) Genotyping for PSMB1 P11A

  Up to 5 years

• Gene Expression Profiling on Tumor Specimens

  Up to 5 years

Study Arms (1)

Treatment (ixazomib citrate, rituximab)

EXPERIMENTAL

Patients receive ixazomib citrate orally (PO) on days 1, 8 ,15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Upon completion of 6 cycles of ixazomib citrate therapy, patients also receive rituximab intravenously (IV) once weekly for 4 doses total, followed by ixazomib citrate alone, until disease progression or unacceptable toxicity.

Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Biological: Rituximab

Interventions

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate, rituximab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83, Rituximab Biosimilar SIBP-02

Treatment (ixazomib citrate, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception)
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
• Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception)
• Patients must have a diagnosis of one of the following B-NHL malignancies: chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or Waldenstrom macroglobulinemia (WM)/ lymphoplasmacytic lymphoma (LPL); patients with mucosa associated lymphoid tissue (MALT) subtype of MZL may have relapsed or refractory disease after a course of antibiotic therapy; otherwise, patients will not have received standard systemic treatment for their B-NHL before the time of study enrollment; standard systemic therapy is defined by including any of the following agents, representing a comprehensive list of recommended front-line agents used in the treatment of B-NHL: cytotoxic chemotherapies (bendamustine, cyclophosphamide, doxorubicin, vincristine, chlorambucil, cytarabine, gemcitabine, platinum drugs, etoposide); anti-CD20 antibodies (obinutuzumab, ofatumumab, rituximab); lenalidomide; ibritumomab tiuxetan; proteasome inhibitors (bortezomib, carfilzomib); tyrosine kinase inhibitors (ibrutinib, acalabrutinib, idelalisib); alemtuzumab; corticosteroids unless given for an indication other than treating the B-NHL; or other therapy as determined by the principal investigator (PI)
• Disease: CLL/SLL; Criteria for diagnosis: histopathologic or flow cytometric confirmation
• Disease: FL; Criteria for diagnosis: histopathologic confirmation
• Disease: MZL; Criteria for diagnosis: histopathologic confirmation
• Disease: MCL; Criteria for diagnosis: histopathologic confirmation
• Disease: WM/LPL; Criteria for diagnosis: Per World Health Organization (WHO) criteria

You may not qualify if:

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Major surgery within 14 days before enrollment
• Known central nervous system involvement
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure, and unstable angina or myocardial infarction within the past 6 months
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (CYP3A) (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort
• Known ongoing or known active systemic infection, known active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Known allergy to ixazomib, its analogues, or excipients in the various formulations of ixazomib
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
• Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed (\> 2 years before study enrollment) with another malignancy and have any evidence of residual disease that is symptomatic or requiring treatment; (this may be waived at the discretion of the principal investigator for patients in complete remission if they have not received systemic therapy); patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
• Patient has \>= grade 2 peripheral neuropathy, or grade 1 with pain on clinical examination during the screening period
• Participation in other clinical trials with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial
• Patients may not have impending organ compromise from disease as assessed by their treating physician
• Prior treatment of B-NHL with radiation therapy, non-standard systemic therapy, or antibiotics (in cases of MZL) within 21 days of the first dose of ixazomib

Sponsors & Collaborators

• University of Washington: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Graf SA, Lynch RC, Ujjani CS, Gooley TA, Rasmussen H, Coffey DG, Cowan AJ, Smith SD, Shadman M, Warren EH, Libby EN, Greninger AL, Fromm JR, Gopal AK. Efficacy, safety, and molecular response predictors of oral ixazomib and short-course rituximab in untreated iNHL. Blood Adv. 2023 Mar 14;7(5):687-696. doi: 10.1182/bloodadvances.2022008628.

  PMID: 36385536 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia

Interventions

ixazomib; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Ajay Gopal, MD
• Organization: University of Washington

agopal@uw.edu

2066062037

Study Officials

• Ajay K. Gopal

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 16, 2015
• Study Start: May 19, 2016
• Primary Completion: December 30, 2024
• Study Completion (Estimated): January 6, 2031
• Last Updated: March 5, 2026
• Results First Posted: March 5, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)