Clinical Trials /

Ph 2 Maintenance Trial: Ixazomib vs Ixazomib-Lenalidomide for MM Patients

NCT03733691

Description:

This is a randomized, Phase 2 study involving two arms evaluating the efficacy and safety of ixazomib alone and the combination of both ixazomib and lenalidomide as maintenance therapy for patients with multiple myeloma who have achieved at least partial response (PR) or better after receiving a bortezomib- and lenalidomide-containing combination front-line therapy.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ph 2 Maintenance Trial: Ixazomib vs Ixazomib-Lenalidomide for MM Patients
  • Official Title: A Phase 2, Open Label, Randomized Trial Evaluating Ixazomib Compared to Ixazomib-Lenalidomide Combination Maintenance Therapy for Frontline Multiple Myeloma Patients

Clinical Trial IDs

  • ORG STUDY ID: X16108
  • NCT ID: NCT03733691

Conditions

  • Newly Diagnosed Multiple Myeloma

Interventions

DrugSynonymsArms
IxazomibNinlaroIxazomib + Lenalidomide
LenalidomideRevlimidIxazomib + Lenalidomide

Purpose

This is a randomized, Phase 2 study involving two arms evaluating the efficacy and safety of ixazomib alone and the combination of both ixazomib and lenalidomide as maintenance therapy for patients with multiple myeloma who have achieved at least partial response (PR) or better after receiving a bortezomib- and lenalidomide-containing combination front-line therapy.

Detailed Description

      Patients who have achieved PR or better on a bortezomib- and lenalidomide-containing
      combination therapy will be randomized to receive maintenance therapy with 28-day cycles of
      either ixazomib alone or the combination of ixazomib and lenalidomide. If steroids were part
      of the patient's qualifying regimen, steroids will be administered using the same drug(s),
      schedule(s) and dose(s) as those of the last treatment cycle of the bortezomib-,
      lenalidomide- and steroid-containing regimen. Ixazomib will be administered per orem (PO) at
      3 mg on days 1, 8 and 15 of 28-day cycles. Lenalidomide will be taken PO, once daily at the
      same dose as the last treatment on days 1 through 28 of the 28-day cycles. Patients will
      start the randomized maintenance therapy after receiving a minimum of 6 cycles of a
      bortezomib- and lenalidomide-containing combination treatment but may have received up to 8
      cycles if they continued to show improvement in their response after the first 6 cycles.
      During cycle 1, patients will have clinical laboratory tests weekly (days 1, 8, 15 and 22)
      and MM disease assessments on day 22 to monitor for efficacy and potential toxicity.
      Beginning with cycle 2, patients will have clinical laboratory tests performed twice a month
      and MM disease assessments once a month. Patients will be treated until documentation of PD
      or if subject meets any of the treatment discontinuation criteria.
    

Trial Arms

NameTypeDescriptionInterventions
Ixazomib OnlyExperimentalThe prescribed dose administration of ixazomib in this study is 3mg orally on Days 1, 8, and 15 of a 28-day cycle.
  • Ixazomib
Ixazomib + LenalidomideExperimentalThe prescribed dose administration of ixazomib in this study is 3mg orally on Days 1, 8, and 15 of a 28-day cycle. The prescribed dose administration of lenalidomide in this study is the same as the dose of the patient's front-line treatment taken in the last treatment cycle unless otherwise clinically indicated per investigator's discretion, taken orally on days 1-28 of a 28-day cycle. If patient was receiving lenalidomide at a higher dose than 10 mg, then the dose of lenalidomide on this study will be adjusted to 10 mg daily on days 1-28 of a 28-day cycle
  • Ixazomib
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

        -

        Each patient must meet all of the following inclusion criteria to be enrolled in the study:

          1. Male or female patients 18 years or older.

          2. Patients must be receiving a frontline bortezomib- and lenalidomide-containing regimen
             for treatment of disease

          3. Patients must meet the following clinical laboratory criteria:

               -  Absolute neutrophil count (ANC) grater or equal 1,000/mm3 and platelet count
                  greater or equal 75,000/mm3. Platelet transfusions to help patients meet
                  eligibility criteria are not allowed within 7 days prior to screening platelets
                  or at investigator's discretion.

               -  Hemoglobin ≥ 8.0 g/dL. Use of erythropoietic stimulating factors and red blood
                  cell (RBC) transfusions per institutional guidelines is allowed; however, most
                  recent RBC transfusion must have been at least 7 days prior to obtaining
                  screening hemoglobin or at investigator's discretion.

               -  Total bilirubin less or equal 1.5 times the upper limit of the normal range
                  (ULN).

               -  Calculated or measured creatinine clearance greater or equal 30 mL/min.
                  Calculation is based on a standard Cockcroft and Gault formula (Section 14.2).

               -  AST (SGOT) and ALT (SGPT) less or equal 3 x ULN or less or equal 5 x ULN if
                  hepatic metastases are present.

               -  LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of
                  evaluation. Mitigated Acquisition Scan (MUGA) is acceptable if ECHO is not
                  available.

          4. Patients must be transplant ineligible as determined by the treating physician.

          5. Patients must have a life-expectancy of more than 6 months.

          6. Patients must have a confirmed diagnosis of MM.

          7. Patients receiving front-line therapy must have achieved at least PR and have
             completed at least 6 cycles of treatment.

          8. The disease must have reached a plateau phase at the end of front-line treatment as
             demonstrated bythe same response (using IMWG criteria) in three consecutive tests with
             at least three weeks between each test.

          9. Patients must have received frontline treatment within 8 weeks of enrollment.

         10. Patient can adhere to the study visit schedule and other protocol requirements.

         11. Patient Eastern Cooperative Oncology Group (ECOG) performance status is ≤ 2.

         12. Patients must voluntarily give written consent before any study related procedure not
             part of standard medical care is performed, with the understanding that consent may be
             withdrawn by the patient at any time without prejudice to future medical care.

         13. Female patients must be postmenopausal for at least 1 year before screening visit OR
             surgically sterile. If patient is female of childbeating potential (FCBP), patient
             must agree to practice two 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. FCBP must also adhere to the guidelines of any treatment-specific
             pregnancy prevention program AND 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.

         14. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree
             to one of the following:

               -  To practice effective barrier contraception during the entire study treatment
                  period and through 90 days after the last dose of study drug

               -  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.

        Exclusion Criteria:

          -  Patients meeting any of the following exclusion criteria are not to be enrolled in the
             study:

               1. Patient is currently progressing on a bortezomib- and lenalidomide-containing
                  regimen.

               2. Patients who have received more than 1 line of therapy (thus non-frontline
                  treated patients).

               3. Patients who were exposed to ixazomib during frontline therapy.

               4. Patient has ¬> Grade 3 peripheral neuropathy or Grade 2 with pain during the
                  screening period.

               5. Patient has known gastrointestinal disease or gastrointestinal procedure that
                  could interfere with the oral absorption or tolerance of ixazomib including
                  difficulty swallowing.

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

               7. Major surgery within 14 days before enrollment or at investigator's discretion.

               8. Patients undergoing stem cell therapy (SCT) or those who are planned for SCT.

               9. Radiotherapy within 14 days before enrollment or investigator's discretion. If
                  the involved field is small, 7 days or investigator's discretion will be
                  considered a sufficient interval between treatment and administration of the
                  study drugs. Receipt of localized radiation therapy does not preclude enrollment.

              10. Infection requiring systemic antibiotic therapy or other serious infection such
                  as known active hepatitis B or C virus infection, known human immunodeficiency
                  virus (HIV) positive within 14 days before of study enrollment or at
                  investigator's discretion.

              11. Evidence of current uncontrolled cardiovascular conditions, including
                  uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic
                  congestive heart failure, NYHA Class III or IV heart failure, unstable angina,
                  clinically significant pericardial disease or myocardial infarction within the
                  past 6 months, unless subject has a pacemaker. Prior to study entry, any ECG
                  abnormality at Screening must be documented by the investigator as not medically
                  relevant.

              12. Frontline therapy within 14 days or at investigator's discretion of the first
                  dose of study drugs.

              13. Systemic treatment, within 14 days before or at investigator's discretion of the
                  first dose of study drugs, with strong CYP3A inducers (rifampin, rifapentine,
                  rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort or
                  Ginkgo biloba.

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

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

              16. 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 non-melanoma skin cancer or carcinoma in situ of any type are not
                  excluded if they have undergone complete resection.

              17. Participation in other clinical trials throughout the duration of this trial.

              18. Patient has been diagnosed with:

                    1. Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,
                       monoclonal protein (M protein) and skin changes (POEMS) syndrome3.

                    2. Primary amyloidosis

                    3. Plasma cell leukemia.

                    4. Severe hypercalcemia, i.e., serum calcium ≥ 12 mg/dL (3.0 mmol/L) corrected
                       for albumin.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:Through study completion, approximately 5 years
Safety Issue:
Description:Progression Free Survival

Secondary Outcome Measures

Measure:OS
Time Frame:from time of initiation of maintenance therapy to death from any cause or last follow-up visit, up to 60 months
Safety Issue:
Description:Overall survival
Measure:Deepening of the response
Time Frame:throughout the study, up to 60 months
Safety Issue:
Description:define as the percentage of patients who improved their response during maintenance therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Oncotherapeutics

Trial Keywords

  • Multiple Myeloma
  • Front-line
  • Maintenance therapy

Last Updated

September 18, 2019