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

Sponsor
Fred Hutchinson Cancer Research Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02619682
Collaborator
(none)
30
Enrollment
1
Location
1
Arm
90
Anticipated Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. Evaluate the toxicity of the use of ixazomib (ixazomib citrate) and lenalidomide as maintenance therapy after autologous transplant.
SECONDARY OBJECTIVES:
  1. Evaluate the ability to deliver the planned therapy.

  2. Assess initial response to therapy.

  3. Evaluate the median time to disease progression.

  4. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Alternating the Administration of Ixazomib and Lenalidomide as Maintenance Therapy After Autologous Transplant for Treating Multiple Myeloma
Actual Study Start Date :
Dec 30, 2015
Anticipated Primary Completion Date :
Feb 1, 2022
Anticipated Study Completion Date :
Jul 1, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (ixazomib citrate and lenalidomide)

Within 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.

Drug: Ixazomib Citrate
Given PO
Other Names:
  • MLN-9708
  • MLN9708
  • Ninlaro
  • Other: Laboratory Biomarker Analysis
    Correlative studies

    Drug: Lenalidomide
    Given PO
    Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events version 4.0 [2 years]

      Toxicity during the 24 months of post-transplant maintenance therapy

    Secondary Outcome Measures

    1. Overall survival [Up to 2 years post-treatment]

    2. Time to disease progression [Up to 2 years post-treatment]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109

    Sponsors and Collaborators

    • Fred Hutchinson Cancer Research Center

    Investigators

    • Principal Investigator: Leona Holmberg, Fred Hutch/University of Washington Cancer Consortium

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fred Hutchinson Cancer Research Center
    ClinicalTrials.gov Identifier:
    NCT02619682
    Other Study ID Numbers:
    • 9266
    • NCI-2015-01861
    • X16064
    • 9266
    • RG9215039
    First Posted:
    Dec 2, 2015
    Last Update Posted:
    Nov 10, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 10, 2021