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

December 12, 2019 updated by: Arbeitsgemeinschaft medikamentoese Tumortherapie

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Austria
      • 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
  • Czechia
      • Brno, Czechia, 639 00
        • Faculty Hospital Brno and Faculty of Medicine MU Brno 2nd Internal Clinic
      • Ostrava-Poruba, Czechia, 708 52
        • Fakultni Nemocnice Ostrava
  • Germany
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Dexamethasone
Drug: Thalidomide
Drug: Ixazomib

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Arbeitsgemeinschaft medikamentoese Tumortherapie

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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.

General Publications

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 28, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 2, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 9, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 12, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AGMT_MM-1

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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