Clinical Trials /

Alternating Ixazomib Citrate and Lenalidomide as Maintenance Therapy After Stem Cell Transplant in Treating Patients With Multiple Myeloma

NCT02619682

Description:

This phase II trial studies the safety of alternating ixazomib citrate and lenalidomide as treatment to help keep cancer from coming back after stem cell transplant (maintenance therapy) in treating patients with multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system to attack cancer cells. Giving ixazomib citrate and lenalidomide as maintenance therapy after transplant may prolong the length of time until the cancer returns.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Alternating Ixazomib Citrate and Lenalidomide as Maintenance Therapy After Stem Cell Transplant in Treating Patients With Multiple Myeloma
  • Official Title: Alternating the Administration of Ixazomib and Lenalidomide as Maintenance Therapy After Autologous Transplant for Treating Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 9266
  • SECONDARY ID: NCI-2015-01861
  • SECONDARY ID: X16064
  • SECONDARY ID: 9266
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG9215039
  • NCT ID: NCT02619682

Conditions

  • Plasma Cell Myeloma
  • Transplant-Related Carcinoma

Interventions

DrugSynonymsArms
Ixazomib CitrateMLN-9708, MLN9708, NinlaroTreatment (ixazomib citrate and lenalidomide)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment (ixazomib citrate and lenalidomide)

Purpose

This phase II trial studies the safety of alternating ixazomib citrate and lenalidomide as treatment to help keep cancer from coming back after stem cell transplant (maintenance therapy) in treating patients with multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stimulate the immune system to attack cancer cells. Giving ixazomib citrate and lenalidomide as maintenance therapy after transplant may prolong the length of time until the cancer returns.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Evaluate the toxicity of the use of ixazomib (ixazomib citrate) and lenalidomide as
      maintenance therapy after autologous transplant.

      SECONDARY OBJECTIVES:

      I. Evaluate the ability to deliver the planned therapy.

      II. Assess initial response to therapy.

      III. Evaluate the median time to disease progression.

      IV. Assess overall survival.

      OUTLINE:

      Within 30-120 days after completion of autologous transplant, patients receive ixazomib
      citrate orally (PO) on days 1, 8 and 15 every 28 days for 2 courses, followed by lenalidomide
      PO once daily (QD) on days 1-28 for 2 courses. Treatment repeats, alternating after every 2
      courses, for up to 24 months 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 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ixazomib citrate and lenalidomide)ExperimentalWithin 30-120 days after finishing autologous transplant, patients receive ixazomib citrate PO on days 1, 8 and 15. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive lenalidomide PO QD on days 1-28. Treatment repeats for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients will continue to alternate between ixazomib citrate and lenalidomide every 2 courses for up to 24 months in the absence of disease progression or unacceptable toxicity.
  • Ixazomib Citrate
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

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

          -  Any autologous patient who underwent high dose melphalan (>= 140 mg/m^2)
             therapy/peripheral blood stem cell (PBSC) rescue for any stage of multiple myeloma and
             did not participate in another clinical transplant trial whose primary endpoint is
             also evaluating long-term, disease-free survival or survival; consenting for study
             between 30 days to 120 days after transplant; earliest can start therapy is 30 days
             post transplant after recovered from acute toxicity of autologous stem cell transplant
             (ASCT)

          -  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)

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

          -  Platelet count (transfusion independent) >= 75,000/mm^3

          -  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

        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 ASCT 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

          -  History of central nervous system multiple myeloma 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, 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
             inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 gene (CYP1A2)
             (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family
             3, subfamily A gene locus (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 any of the study medications, their analogues, or excipients in the
             various formulations of any agent; patient cannot be allergic to boron

          -  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 2 peripheral neuropathy, or grade 1 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 with history prior to transplant of progression on lenalidomide therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events version 4.0
Time Frame:4 months
Safety Issue:
Description:The first four months of therapy will be used as the time period in which toxicity will be evaluated and stopping rules for unacceptable toxicity will be implemented. A true withdrawal rate within first 4 months of 15% will be considered excessive. The incidence of second cancers will also be collected.

Secondary Outcome Measures

Measure:Overall survival
Time Frame:Up to 2 years post-treatment
Safety Issue:
Description:
Measure:Time to disease progression
Time Frame:Up to 2 years post-treatment
Safety Issue:
Description:Response criteria will be determined by International Myeloma Working Group Criteria. In patients with chemo-refractory disease at the time of ASCT, the therapy will be felt to be promising if median time to progression is > 9 months. If chemo-sensitive disease at time of ASCT, the therapy will be felt to be promising if median time to progression is > 41 months based on Cancer and Leukemia Group B (CALGB) 10014 lenalidomide maintenance study post ASCT. Initial response rates and outcome will be descriptively reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Fred Hutchinson Cancer Research Center

Last Updated

October 23, 2019