Clinical Trials /

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

NCT02339922

Description:

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. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib Citrate and Rituximab in Treating Patients With Indolent B-cell Non-Hodgkin Lymphoma
  • Official Title: A Window Study of Ixazomib in Untreated Indolent B-NHL

Clinical Trial IDs

  • ORG STUDY ID: 9571
  • SECONDARY ID: NCI-2016-00401
  • SECONDARY ID: 9224
  • SECONDARY ID: 9571
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG1716009
  • NCT ID: NCT02339922

Conditions

  • 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

Interventions

DrugSynonymsArms
Ixazomib CitrateMLN-9708, MLN9708, NinlaroTreatment (ixazomib citrate, rituximab)
RituximabABP 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, RTXM83Treatment (ixazomib citrate, rituximab)

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. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib citrate together with rituximab may work better in treating indolent B-cell non-Hodgkin lymphoma.

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/EXPLORATORY 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. Upon completion of 6
      courses of ixazomib citrate therapy, patients also receive rituximab intravenously (IV) once
      weekly. Courses repeat every 28 days 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 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ixazomib citrate, rituximab)ExperimentalPatients receive ixazomib citrate PO once weekly every 4 weeks. Upon completion of 6 courses of ixazomib citrate therapy, patients also receive rituximab IV once weekly. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Ixazomib Citrate
  • Rituximab

Eligibility 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 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

          -  Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance
             status 0, 1, or 2

          -  Absolute neutrophil count (ANC) > 1,000/mm^3 or > 500/mm^3 if neutropenia is
             attributed to B-NHL (involvement of bone marrow) without growth factor support and
             platelet count > 100,000/mm3 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

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Overall survival
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:CR rate
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:Data for subjects that have not received additional anti-neoplastic therapy will be censored at the date of last known contact.
Measure:Incidence of adverse events (AEs)
Time Frame:Up to 30 days after administration of the last dose of ixazomib citrate
Safety Issue:
Description:Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. 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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

January 16, 2020