Clinical Trials /

Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

NCT04047797

Description:

This phase II trial studies how well ixazomib and rituximab work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond (refractory) to BTK inhibitor treatment. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with rituximab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib and rituximab may work better in treating patients with mantle cell lymphoma compared to rituximab alone.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma
  • Official Title: A Phase 2 Study of Ixazomib and Rituximab in Bruton Tyrosine Kinase Inhibitor Resistant Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 2018-1090
  • SECONDARY ID: NCI-2019-04857
  • SECONDARY ID: 2018-1090
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04047797

Conditions

  • Recurrent Mantle Cell Lymphoma
  • Refractory Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
IxazomibMLN-2238, MLN2238Treatment (ixazomib, rituximab)
Ixazomib CitrateMLN-9708, MLN9708, NinlaroTreatment (ixazomib, 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, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, TruximaTreatment (ixazomib, rituximab)

Purpose

This phase II trial studies how well ixazomib and rituximab work in treating patients with mantle cell lymphoma that has come back (relapsed) or does not respond (refractory) to BTK inhibitor treatment. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with rituximab may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving ixazomib and rituximab may work better in treating patients with mantle cell lymphoma compared to rituximab alone.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the complete remission rate of Bruton's tyrosine kinase (BTK) inhibitor
      refractory mantle cell lymphoma (MCL) patients with ixazomib citrate (ixazomib) and rituximab
      at 16 weeks of therapy.

      SECONDARY OBJECTIVES:

      I. To evaluate overall response rate (ORR) assessed by Lugano criteria. II. To evaluate
      progression free survival (PFS) and overall survival (OS). III. To evaluate the safety and
      tolerability.

      TERTIARY/EXPLORATORY OBJECTIVES:

      I. To evaluate biomarkers of response to treatment and mechanisms of resistance with
      pretreatment and post-treatment bone marrow and blood samples with deoxyribonucleic acid
      (DNA) and ribonucleic acid (RNA) sequencing and immune profiling by flow cytometry.

      OUTLINE:

      Patients receive ixazomib orally (PO) on days 1, 8, and 15. Treatment repeats every 28 days
      for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients
      also receive rituximab intravenously (IV) over 4-8 hours on days 1, 8, 15, and 22 of cycle 1.
      Beginning in cycle 3, patients receive rituximab IV over 4-8 hours on day 1. Treatment
      repeats every 28 days up to cycle 12 in the absence of disease progression or unacceptable
      toxicity. Patients benefiting from treatment may continue to receive ixazomib indefinitely in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ixazomib, rituximab)ExperimentalPatients receive ixazomib by mouth on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of cycle 1. Beginning in cycle 3, patients receive rituximab Intravenous over 4-8 hours on day 1. Treatment repeats every 28 days up to cycle 12 in the absence of disease progression or unacceptable toxicity. Patients benefiting from treatment may continue to receive ixazomib indefinitely in the absence of disease progression or unacceptable toxicity.
  • Ixazomib
  • Ixazomib Citrate
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have histologically confirmed diagnosis of mantle cell lymphoma

          -  Patients must have measurable disease, as defined by at least one of the following:

               -  Lymph node or mass 2 cm or greater, splenomegaly > 13 cm

               -  Bone marrow only disease as per morphology or flow cytometry

          -  Patients must have relapsed and/or refractory disease to at least 2 lines of therapy
             including either an anthracycline- or bendamustine- based regimen and a BTK inhibitor

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

          -  Absolute neutrophil count (ANC) >= 1,000/mm^3

          -  Platelets >= 50,000/mm^3

          -  Total bilirubin < 1.5 x institutional upper limit of normal (ULN). In patients with
             documented Gilbert's syndrome, total bilirubin =< 2.5 x ULN

          -  Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and
             alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) =< 3 x ULN

          -  Creatinine clearance >= 30 mL/min

          -  Patients must be willing to give written consent before performance of any study
             related procedures 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

          -  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

        Exclusion Criteria:

          -  Female patients who are lactating or have a positive serum pregnancy test during the
             screening period

          -  Failure to have fully recovered (i.e., =< grade 1 toxicity) from the reversible
             effects of prior chemotherapy

          -  Major surgery within 14 days before enrollment

          -  Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days
             will be considered a sufficient interval between treatment and administration of the
             ixazomib

          -  Central nervous system involvement

          -  Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before study enrollment. Patient may be eligible, if infectious disease
             specialist approves start of therapy AND subject has completed course of antibiotic
             therapy

          -  Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months

          -  Systemic treatment, within 14 days before the first dose of ixazomib, with strong
             CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin,
             phenobarbital), or use of St. John's wort

          -  Ongoing or active systemic infection, active (deoxyribonucleic acid [DNA] polymerase
             chain reaction [PCR] positivity) 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 any of the study medications, their analogues, or excipients in the
             various formulations of any agent

          -  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 with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection

          -  Patient has >= grade 3 peripheral neuropathy, or grade 2 with pain on clinical
             examination during the screening period

          -  Participation in other clinical trials, including those with other investigational
             agents not included in this trial, within 30 days of the start of this trial and
             throughout the duration of this trial

          -  Patients that have previously been treated with proteasome inhibitors, or participated
             in a study with proteasome inhibitors whether treated with proteasome inhibitors or
             not
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete remission rate of BTK inhibitor refractory mantle cell lymphoma patients with ixazomib and rituximab
Time Frame:At 16 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:At 16 weeks
Safety Issue:
Description:Assessed by Lugano criteria. Overall response and complete response at each of the pre-specified time points will be described as percentage with exact ninety-five percent (95%) confidence interval based on binomial distribution.
Measure:Progression free survival (PFS)
Time Frame:From the start date of treatment to the date of progression or death due to any cause whichever happened first, assessed up to 1 year
Safety Issue:
Description:PFS curves will be described using Kaplan-Meier methods. The curves will be presented with 95% confidence intervals.
Measure:Overall survival (OS)
Time Frame:From the start date of treatment to death date, assessed up to 1 year
Safety Issue:
Description:OS curves will be described using Kaplan-Meier methods. The curves will be presented with 95% confidence intervals.
Measure:Incidence of toxicities
Time Frame:Up to 56 weeks
Safety Issue:
Description:Toxicities will be measured using Common Terminology Criteria for Adverse Events version 4.0. The maximum grade of each toxicity will be described in tabular form as count and percentages.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated