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

This study is currently recruiting participants.
Verified January 2017 by University of Washington
Sponsor:
ClinicalTrials.gov Identifier:
NCT02339922
First Posted: January 16, 2015
Last Update Posted: January 13, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington
  Purpose
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. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.

Condition Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Window Study of Ixazomib in Untreated Indolent B-NHL

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • ORR (CR + very good PR + PR + minor response) in patients with WM/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 CLL/SLL, FL, MZL, and 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.


Secondary Outcome Measures:
  • CR rate [ Time Frame: Up to 5 years ]
  • 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 ]
  • 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.

  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 36
Study Start Date: May 2016
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given PO
Other Names:
  • MLN-9708
  • MLN9708
  • Ninlaro
Other: Laboratory Biomarker Analysis
Correlative studies
Biological: Rituximab
Given IV
Other Names:
  • 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 PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

I. To evaluate clinical and biological prognostic and predictive biomarkers relative to treatment outcomes of ixazomib in indolent B-NHL.

OUTLINE:

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 systemic treatment for their B-NHL before the time of study enrollment

    • 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
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1,000/mm^3 without growth factor support
  • Platelet count >= 100,000/mm^3 or >= 75,000/mm^3 if thrombocytopenia is attributed to B-NHL (involvement of bone marrow or due to splenomegaly or immune thrombocytopenic purpura); platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
  • Total bilirubin =<1.5 x the upper limit of the normal range (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • Calculated creatinine clearance >= 30 mL/min
  • Patients are required to meet criteria for initiation of therapy for their B-NHL according to published guidelines by the National Comprehensive Cancer Network (NCCN)
  • Patients must have measurable disease defined by at least one of the following criteria:

    • Lesions greater than 1.5 cm that can be accurately measured in two dimensions by computed tomography (CT) (preferred), or magnetic resonance imaging (MRI), and are not included in any prior field of radiation given to treat B-NHL
    • In patients with CLL, circulating lymphocytes >= 5,000 / mm^3
    • In patients with WM/LPL, measurable serum monoclonal immunoglobulin M (IgM)

Exclusion Criteria:

  • 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
  • Ongoing or active systemic infection, 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; 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 or antibiotics (in cases of MZL) within 21 days of the first dose of ixazomib
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339922


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal    206-288-2037    agopal@u.washington.edu   
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT02339922     History of Changes
Other Study ID Numbers: 9571
NCI-2016-00401 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9224
9571 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: December 30, 2014
First Posted: January 16, 2015
Last Update Posted: January 13, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia
Leukemia, B-Cell
Lymphoma, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Ixazomib
Rituximab
Antibodies
Immunoglobulins
Antibodies, Monoclonal