Ixazomib in Combination With Thalidomide - Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

Overview of Study Design:

This is an open phase II, single-arm, multi-center study to evaluate progression free survival in patients receiving ixazomib in combination with thalidomide and dexamethasone (ITD) followed by an ixazomib maintenance phase of a maximum period of 12 months.

The patient population will consist of adult male and female patients with multiple myeloma (MM) with relapsed and/or refractory disease after at least one prior treatment line.

In case of enrollment patients will receive ixazomib 4.0mg at days 1, 8, 15, thalidomide 100mg at days 1 to 28 (50mg in patients aged ≥75 years), and dexamethasone 40mg (20mg in patients aged ≥75 years) at days 1, 8, 15 of a 28-day treatment cycle. The proposed number of cycles is 8. Treatment will be discontinued in case of progressive disease or in case of no response after 4 cycles (≤ SD after 4 cycles). After discontinuation of therapy an end of treatment visit (EOT) will be performed within 14 days after the last dose of the last combination treatment cycle.

After 8 cycles of ITD therapy, maintenance treatment with 4.0mg ixazomib (3.0mg in patients aged ≥ 75 years at first day of maintenance phase) on days 1, 8, 15 of 28-day cycles will be administered to patients with ≥ MR for a maximum period of 12 months. Patients who completed less than 8 cycles of ITD treatment do not qualify for maintenance phase.

Follow-up visits will be performed in 3-monthly intervals until the last patient on ixazomib maintenance therapy has concluded or discontinued the maintenance phase.

A safety analysis will be conducted after enrollment of the first 6 patients and completion of at least two cycles in every patient.

Study Overview

Status

Completed

Conditions

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Linz, Austria, 4021
        • Kepler Universitätsklinikum Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinische Onkologie
      • Salzburg, Austria, 5020
        • Universitätsklinik der PMU Universitätsklinik für Innere Medizin III
      • Vienna, Austria, A-1160
        • Wilhelminenspital
      • Wien, Austria, 1020
        • KH der Barmherzigen Brüder Wien, Innere Medizin
      • Wien, Austria, 1090
        • Med. Universität Wien, Universitätsklinik f. Innere Medizin I, Klin. Abt. f. Hämatologie u. Hämostaseologie
    • Oberösterreich
      • Linz, Oberösterreich, Austria, 4010
        • Ordensklinikum, KH der Barmherzigen Schwestern Linz, Interne I: Internistische Onkologie, Hämatologie und Gastroenterologie
      • Linz, Oberösterreich, Austria, 4020
        • KH der Elisabethinen Linz, 1. Interne Abteilung
      • Wels, Oberösterreich, Austria, 4600
        • Klinikum Wels-Grieskirchen, IV. Interne Abteilung
    • Steiermark
      • Graz, Steiermark, Austria, 8036
        • Medizinische Universitätsklinik Graz, Klinische Abteilung für Hämatologie
    • Tirol
      • Innsbruck, Tirol, Austria, 6020
        • UK Innsbruck, Universitätsklinik für Innere Medizin, Klinische Abteilung für Hämatologie und Onkologie
      • Kufstein, Tirol, Austria, 6330
        • A.ö. BK Kufstein, Abteilung für Innere Medizin
    • Vorarlberg
      • Feldkirch, Vorarlberg, Austria, 6830
        • LKH Feldkirch, Interne E
      • Brno, Czechia, 639 00
        • Faculty Hospital Brno and Faculty of Medicine MU Brno 2nd Internal Clinic
      • Ostrava-Poruba, Czechia, 708 52
        • Fakultni nemocnice Ostrava
      • Leipzig, Germany, 04103
        • Universitätsklinikum Leipzig - AöR Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie
      • Tubingen, Germany, 72076
        • Universitätsklinikum Tübingen, Innere Medizin II
      • Wurzburg, Germany, 97080
        • Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum Innere Medizin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female patients 18 yrs or older.
  2. Voluntary written consent
  3. Patients in need of therapy with a diagnosis of relapsed or refractory multiple myeloma who had at least one prior treatment line
  4. Patients must have measurable disease defined by at least 1 of the following criteria:

    • Serum M-protein ≥ 10g/l
    • Urine M-protein ≥ 200mg/24h
    • Serum free light chain assay: involved serum light chain ≥ 10mg/dl provided that free light chain ration is abnormal
  5. Life expectancy > 3 months
  6. ECOG (Eastern Cooperative Oncology Group) ≤ 2
  7. • ANC ≥ 1.000/mm3 and platelet count ≥ 50.000/mm3

    • Total bilirubin ≤ 2 x ULN
    • ALT and AST ≤ 3 x ULN
    • GFR ≥ 15ml/min as calculated by cockroft-Gault equation
  8. Female patients who:

    • Are older than 50 years and 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 4 weeks before starting study therapy 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.)
    • Are informed and understand the possible consequences of the teratogenic potential of thalidomide
    • 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.)
    • Are informed and understand the possible consequences of the teratogenic potential of thalidomide
  9. Disease free of prior malignancies for ≥ 2 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast if they have undergone complete resection.

Exclusion Criteria:

  1. lactating females or have a positive serum pregnancy test
  2. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy
  3. Previous treatment with ixazomib
  4. Previous treatment with bortezomib or thalidomide within the last 3 months prior to baseline visit
  5. Primary refractory to, or relapsing during, or within ≤ 6 weeks after end of treatment with a proteasome inhibitor and/or thalidomide
  6. Previous anti-cancer treatment within the last 21 days prior to baseline visit (cycle 1 / day 1), except corticosteroid therapy (40 - 160mg dexamethasone or corticosteroid dose equivalent per month)
  7. Major surgery within 14 days before enrollment
  8. 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.
  9. Central nervous system involvement
  10. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
  11. Evidence of current uncontrolled cardiovascular conditions
  12. Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of 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
  13. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  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. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
  17. 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 basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast with are not excluded if they have undergone complete resection
  18. Patient has ≥ Grade 3 peripheral neuropathy or Grade 2 with pain on clinical examination during the screening period
  19. Participation in other interventional 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Ixazomib-Thalidomide-Dexamethasone

Combination therapy of:

Ixazomib 4.0mg at days 1, 8, 15, Thalidomide 100mg at days 1 to 28 (50mg in patients aged ≥75 years), Dexamethasone 40mg (20mg in patients aged ≥75 years) at days 1, 8, 15 of a 28-day treatment cycle.

After 8 cycles of ITD therapy, maintenance treatment with 4.0mg ixazomib (3.0mg in patients aged ≥ 75 years at first day of maintenance phase) on days 1, 8, 15 of 28-day cycles will be administered to patients with ≥ MR for a maximum period of 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression free survival (PFS)
Time Frame: start of combination therapy to progressive disease or death due to any cause whichever occurs first, up to 4.5 years
start of combination therapy to progressive disease or death due to any cause whichever occurs first, up to 4.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: best and first response since start of therapy, up to 4,5 years
best and first response since start of therapy, up to 4,5 years
Overall Survival (OS)
Time Frame: start of therapy to death, up to 4,5 years
start of therapy to death, up to 4,5 years
Renal Response in a subgroup of patients with baseline GFR 15-30ml/min
Time Frame: start of therapy to best renal response, up to 4,5 years
start of therapy to best renal response, up to 4,5 years
Determination of safety by reporting of adverse events
Time Frame: start of therapy to end of study therapy (appr. 2 yrs)
Reporting of adverse event as a measure of safety and tolerability
start of therapy to end of study therapy (appr. 2 yrs)
Assessment of prognostic values of risk factors at diagnosis incl. clinical assessment and cytogenetic abnormalities
Time Frame: screening to end of study (appr. 2 yrs)
screening to end of study (appr. 2 yrs)
Correlation between altered expressions of specifically selected genes and patient´s response to the treatment regimen
Time Frame: screening to end of study (appr. 2 yrs)
screening to end of study (appr. 2 yrs)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Heinz Ludwig, MD, Wilhelminenspital Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 1, 2015

Primary Completion (ACTUAL)

March 28, 2019

Study Completion (ACTUAL)

May 2, 2019

Study Registration Dates

First Submitted

February 9, 2015

First Submitted That Met QC Criteria

April 2, 2015

First Posted (ESTIMATE)

April 8, 2015

Study Record Updates

Last Update Posted (ACTUAL)

December 13, 2019

Last Update Submitted That Met QC Criteria

December 12, 2019

Last Verified

December 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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