Clinical Trials /

Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma(MCL)

NCT03616782

Description:

1. Induction chemotherapy 1) RCHOP(Rituximab+Cyclophosphamide+Doxorubicin+Vincristine+Prednisone) 2) VR-CAP (Bortezomib+Rituximab+Cyclophosphamide+Doxorubicin+Prednisone) Patients who have received induction chemotherapy will be evaluated for responses and those who achieved more than PR(Partial response) or PR will be eligible for this study after receiving informed consents. 2. Experimental step Maintenance ixazomib beginning at least 8 weeks after completion of induction chemotherapy, patients receive ixazomib per oral 3 mg on day 1, 8, and 15 for 4 weeks. And the dose of ixazomib can be escalated to 4mg by response such as partial response or MRD positive. Treatment repeats every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients are screened and sign the informed consent after completion induction chemotherapy (RCHOP or VR-CAP) with more than PR or PR confirmed. It is likely to take approximately 8 weeks in performing above procedures. Patients start maintenance therapy at least 8 weeks and also can be allowed for the extension of 4 weeks because of delayed response evaluation, recovery toxicities of chemotherapy, and official process including agree with informed consent. Recently, ongoing studies about maintenance therapy in lymphoma have window periods of 8-12 weeks. Ixazomib maintenance should continue for 2 years.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma(MCL)
  • Official Title: Multicenter Phase II Study of Ixazomib Maintenance in Patients With Newly Diagnosed Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: FIXATION
  • NCT ID: NCT03616782

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
IxazomibIxazomib

Purpose

1. Induction chemotherapy 1) RCHOP(Rituximab+Cyclophosphamide+Doxorubicin+Vincristine+Prednisone) 2) VR-CAP (Bortezomib+Rituximab+Cyclophosphamide+Doxorubicin+Prednisone) Patients who have received induction chemotherapy will be evaluated for responses and those who achieved more than PR(Partial response) or PR will be eligible for this study after receiving informed consents. 2. Experimental step Maintenance ixazomib beginning at least 8 weeks after completion of induction chemotherapy, patients receive ixazomib per oral 3 mg on day 1, 8, and 15 for 4 weeks. And the dose of ixazomib can be escalated to 4mg by response such as partial response or MRD positive. Treatment repeats every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity. Patients are screened and sign the informed consent after completion induction chemotherapy (RCHOP or VR-CAP) with more than PR or PR confirmed. It is likely to take approximately 8 weeks in performing above procedures. Patients start maintenance therapy at least 8 weeks and also can be allowed for the extension of 4 weeks because of delayed response evaluation, recovery toxicities of chemotherapy, and official process including agree with informed consent. Recently, ongoing studies about maintenance therapy in lymphoma have window periods of 8-12 weeks. Ixazomib maintenance should continue for 2 years.

Detailed Description

      1. Induction chemotherapy 1) RCHOP: Before enrollments, patients receive comprising R-CHOP,
           as induction therapy, comprised rituximab (at a dose of 375 mg per square meter of
           body-surface area), cyclophosphamide (750 mg per square meter), doxorubicin (50 mg per
           square meter), vincristine (1.4mg per square meter) administered on days 1, and oral
           prednisone (100 mg per square meter) administered on days 1 to 5. Patients also receive
           pegylated granulocyte-colonly stimulating factor (G-CSF) subcutaneously (SC) on day 2 to
           day 5. Treatment repeats every 21 days for up to 6 courses in the absence of disease
           progression or unacceptable toxicity.

           VR-CAP: Before enrollments, patients receive comprising VR-CAP, as induction therapy,
           comprised bortezomib (1.3 mg per square meter of body-surface area) administered on days
           1, 4, 8, 11, rituximab (at a dose of 375 mg per square meter), cyclophosphamide (750 mg
           per square meter), doxorubicin (50 mg per square meter) administered on days 1, and oral
           prednisone (100 mg per square meter) administered on days 1 to 5. Patients also receive
           pegylated G-CSF SC on day 2 to day 5. Treatment repeats every 21 days for up to 6
           courses in the absence of disease progression or unacceptable toxicity.

           Patients who have received induction chemotherapy will be evaluated for responses and
           those who achieved more than PR(Partial response) or PR will be eligible for this study
           after receiving informed consents.

        2. Experimental step Maintenance ixazomib beginning at least 8 weeks after completion of
           induction chemotherapy, patients receive ixazomib per oral 3 mg on day 1, 8, and 15 for
           4 weeks. And the dose of ixazomib can be escalated to 4mg by response such as partial
           response or MTD(Maximum Tolerated Dose) positive. Treatment repeats every 4 weeks for up
           to 24 months in the absence of disease progression or unacceptable toxicity.

      Patients are screened and sign the informed consent after completion induction chemotherapy
      (RCHOP or VR-CAP) with more than PR or PR confirmed. It is likely to take approximately 8
      weeks in performing above procedures.

      Patients start maintenance therapy at least 8 weeks and also can be allowed for the extension
      of 4 weeks because of delayed response evaluation, recovery toxicities of chemotherapy, and
      official process including agree with informed consent. Recently, ongoing studies about
      maintenance therapy in lymphoma have window periods of 8-12 weeks.

      Ixazomib maintenance should continue for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
IxazomibExperimentalIxazomib 3mg on day a, 8, 15 q 4 weeks for 24 months or until to progression
  • Ixazomib

Eligibility Criteria

        Inclusion Criteria:

          1. Male or female patients aged ≥19 years

          2. Histologically confirmed mantle cell lymphoma (MCL) meeting the following criteria:
             determined by histology and either expression of cyclin D1 (in association with CD20
             and CD5) or evidence of t(11;14) translocation (by cytogenetics, fluorescence in-situ
             hybridization, or polymerase chain reaction)

          3. In all patients, a paraffin-embedded biopsy tissue block or slides (preferably of
             lymph node origin or bone marrow) was sent to central laboratories (Diagnostic
             Cytology Laboratories or department of pathology) for confirmation of diagnosis of
             MCL.

          4. Stage II, III, or IV

          5. Patients who received RCHOP or VR-CAP induction chemotherapy for 6 cycles confirmed
             response as more than PR or PR after induction therapy and who are ineligible for
             transplantation. .

          6. No clinical evidence of central nervous system (CNS) involvement by lymphoma

          7. Patients must have measurable disease; CT scans at baseline are required to define the
             extent of measurable disease; the scans must be obtained within 6 weeks prior to
             registration; combined CT/PET scans may be used for the baseline and subsequent
             evaluations if accurate tumor measurements can be obtained from the CT component

          8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          9. Absolute neutrophil count (ANC) > 1,000 mm^3 (unless low count due to marrow
             involvement or splenomegaly)

         10. Platelets > 75,000 mm^3 (unless low counts due to marrow involvement or splenomegaly)

         11. Creatinine clearance of ≥ 30 mL/min

         12. Total bilirubin ≤ 1.5 x the upper limit of normal (may be up to 3.0 mg/dL if due to
             Gilbert's disease or due to liver involvement by lymphoma), alanine transaminase level
             ≤3 times the upper limit of normal; aspartate transaminase level ≤3 times the upper
             limit of normal

         13. Patients over the age of 45 must have a left ventricular ejection fraction (LVEF) of
             greater than 45% documented within 90 days prior to registration

         14. Female patients had to be post-menopausal for ≥1 year, surgically sterile, or
             practicing an effective method of birth control (as described in the protocol), and
             have a negative serum beta-human chorionic gonadotropin or urine pregnancy test at
             screening; they also had to agree to continue using birth control measures for ≥6
             months after terminating treatment. Male patients had to agree to use an acceptable
             method of contraception for the duration of the study.

        Exclusion Criteria:

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

          2. Grade 2 or higher baseline peripheral neuropathy

          3. Major surgery within 14 days before enrollment.

          4. 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.

          5. Central nervous system involvement.

          6. Infection requiring systemic antibiotic therapy or other serious infection within 14
             days before study enrollment.

          7. 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.

          8. 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.

          9. Active systemic infection requiring treatment, a known diagnosis of human HIV, or
             active hepatitis B (hepatitis B carriers were permitted)

         10. Any serious medical or psychiatric illness that could, in the investigator's opinion,
             potentially interfere with the completion of treatment according to this protocol.

         11. Known allergy to any of the study medications, their analogues, or excipients in the
             various formulations of any agent.

         12. Known gastrointestinal(GI) disease or GI procedure that could interfere with the oral
             absorption or tolerance of ixazomib including difficulty swallowing.

         13. 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.

         14. Patient has more than Grade 2 peripheral neuropathy on clinical examination during the
             screening period.

         15. 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.

         16. Patients that have previously been treated with ixazomib, or participated in a study
             with ixazomib whether treated with ixazomib or not.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:2-year PFS rates in adult patients with newly diagnosed Mantle Cell Lymphoma
Time Frame:2years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete Response (CR) achievement rates after ixazomib maintenance by Lugano classification
Time Frame:an average of 2 year
Safety Issue:
Description:
Measure:Overall survival (OS) rates at 2 years
Time Frame:2years
Safety Issue:
Description:overall survival of patients with Mantle Cell Lymphoma
Measure:Adverse events (AEs)
Time Frame:2years
Safety Issue:
Description:Adverse events will be measured by the CTCAE scale, version 4.03
Measure:Time to relapse/progression
Time Frame:2years
Safety Issue:
Description:Time to progression is measured from the date of start of study to the date of relapse/progression
Measure:Time to next therapy (TTNT)
Time Frame:2years
Safety Issue:
Description:
Measure:Minimal residual disease (MRD) by IgH or IgK NGS from BM, lymphoma tissue at the baseline and then peripheral blood (cell free DNA).
Time Frame:Screening, 24weeks, 4weeks after end of treatment
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ho Sup Lee

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