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Multiple MyelomaPhase 2NCT02410694

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

A Phase 2 study testing Ixazomib, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 17 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Ixazomib, Thalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
17 sitesin 3 countries
Study dates
Apr 2015to 2 May 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients 18 yrs or older.
  • Voluntary written consent
  • Patients in need of therapy with a diagnosis of relapsed or refractory multiple myeloma who had at least one prior treatment line
  • Patients must have measurable disease defined by at least 1 of the following criteria:
  • Serum M-protein ≥ 10g/l
  • Urine M-protein ≥ 200mg/24h
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  • Serum free light chain assay: involved serum light chain ≥ 10mg/dl provided that free light chain ration is abnormal
  • Life expectancy > 3 months
  • ECOG (Eastern Cooperative Oncology Group) ≤ 2
  • • 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
  • 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
  • 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.

Who cannot join

  • lactating females or have a positive serum pregnancy test
  • Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy
  • Previous treatment with ixazomib
  • Previous treatment with bortezomib or thalidomide within the last 3 months prior to baseline visit
  • Primary refractory to, or relapsing during, or within ≤ 6 weeks after end of treatment with a proteasome inhibitor and/or thalidomide
  • 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)
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  • 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.
  • Central nervous system involvement
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
  • Evidence of current uncontrolled cardiovascular conditions
  • 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
  • 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
  • Known 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 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
  • Patient has ≥ Grade 3 peripheral neuropathy or Grade 2 with pain on clinical examination during the screening period
  • 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

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

Austria12 sites

  • LKH Feldkirch, Interne E

    Feldkirch, Vorarlberg, 6830

  • Medizinische Universitätsklinik Graz, Klinische Abteilung für Hämatologie

    Graz, Styria, 8036

  • UK Innsbruck, Universitätsklinik für Innere Medizin, Klinische Abteilung für Hämatologie und Onkologie

    Innsbruck, Tyrol, 6020

  • A.ö. BK Kufstein, Abteilung für Innere Medizin

    Kufstein, Tyrol, 6330

  • Ordensklinikum, KH der Barmherzigen Schwestern Linz, Interne I: Internistische Onkologie, Hämatologie und Gastroenterologie

    Linz, Upper Austria, 4010

  • KH der Elisabethinen Linz, 1. Interne Abteilung

    Linz, Upper Austria, 4020

  • Kepler Universitätsklinikum Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinische Onkologie

    Linz, 4021

  • Universitätsklinik der PMU Universitätsklinik für Innere Medizin III

    Salzburg, 5020

  • KH der Barmherzigen Brüder Wien, Innere Medizin

    Vienna, 1020

  • Med. Universität Wien, Universitätsklinik f. Innere Medizin I, Klin. Abt. f. Hämatologie u. Hämostaseologie

    Vienna, 1090

  • Wilhelminenspital

    Vienna, A-1160

  • Klinikum Wels-Grieskirchen, IV. Interne Abteilung

    Wels, Upper Austria, 4600

Other trials in Austria

Germany3 sites

  • Universitätsklinikum Leipzig - AöR Selbstständige Abteilung für Hämatologie, Internistische Onkologie und Hämostaseologie

    Leipzig, 04103

  • Universitätsklinikum Tübingen, Innere Medizin II

    Tübingen, 72076

  • Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum Innere Medizin

    Würzburg, 97080

Other trials in Germany

Czechia2 sites

  • Faculty Hospital Brno and Faculty of Medicine MU Brno 2nd Internal Clinic

    Brno, 639 00

  • Fakultní nemocnice Ostrava

    Ostrava-Poruba, 708 52

Other trials in Czechia

About this study

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.

Read more

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.

Being tested
Ixazomib, Thalidomide, Dexamethasone
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02410694
Study groupRoleWhat they receive
Ixazomib-Thalidomide-DexamethasoneExperimentalCombination 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.
Receives: Drug: Ixazomib; Drug: Thalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    Measured: start of combination therapy to progressive disease or death due to any cause whichever occurs first, up to 4.5 years

Secondary outcomes (6)

  1. Overall Response Rate (ORR)

    Measured: best and first response since start of therapy, up to 4,5 years

  2. Overall Survival (OS)

    Measured: start of therapy to death, up to 4,5 years

  3. Renal Response in a subgroup of patients with baseline GFR 15-30ml/min

    Measured: start of therapy to best renal response, up to 4,5 years

  4. Determination of safety by reporting of adverse events

    Reporting of adverse event as a measure of safety and tolerability

    Measured: start of therapy to end of study therapy (appr. 2 yrs)

  5. Assessment of prognostic values of risk factors at diagnosis incl. clinical assessment and cytogenetic abnormalities

    Measured: screening to end of study (appr. 2 yrs)

  6. Correlation between altered expressions of specifically selected genes and patient´s response to the treatment regimen

    Measured: screening to end of study (appr. 2 yrs)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2015 (estimated)
  2. Study startApr 2015
  3. Primary completion28 Mar 2019
  4. Study completion2 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02410694
Sponsor's protocol ID
AGMT_MM-1
Status last verified
Dec 2019
First submitted
9 Feb 2015
Last updated
13 Dec 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Ludwig H, Poenisch W, Knop S, Egle A, Schreder M, Lechner D, Hajek R, Gunsilius E, Krenosz KJ, Petzer A, Weisel K, Niederwieser D, Einsele H, Willenbacher W, Melchardt T, Greil R, Zojer N. Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Br J Cancer. 2019 Oct;121(9):751-757. doi: 10.1038/s41416-019-0581-8. Epub 2019 Sep 27.

    PubMed 31558804

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ixazomib, Thalidomide and Dexamethasone in people with Multiple Myeloma, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Austria, Germany, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02410694, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Dec 2019.

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