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Multiple MyelomaPhase 2NCT03439293

A Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)

A Phase 2 study testing Ixazomib, Daratumumab and Dexamethasone in people with Multiple Myeloma, run by Takeda at 28 sites in 6 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the percentage of participants with a response of very good partial response (VGPR) or better to IDd treatment. 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, Daratumumab and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
28 sitesin 6 countries
Study dates
13 Mar 2018to 26 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Have measurable disease by at least 1 of the following measurements:
  • serum M-protein >=1 gram per liter (g/dL) (>=10 g/L).
  • urine M-protein >=200 mg/24 hours.
  • Have documented evidence of PD on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [example, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).
  • Have achieved a response (partial response (PR) or better) to at least 1 prior therapy.
  • Have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2.
Show all 12Show fewer
  • Must meet the following laboratory criteria:
  • Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3).
  • Platelet count >=75,000/mm^3.
  • Total bilirubin less than or equal to (<=) 1.5*the upper limit of the normal range (ULN) (except for Gilbert syndrome: direct bilirubin <=2*ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=3*ULN.
  • Calculated creatinine clearance >=50 mL/min.

Who cannot join

  • Have undergone prior allogenic bone marrow transplantation.
  • Have received prior ixazomib at any time or daratumumab or other anti-CD38 therapies, except as part of initial therapy if this was stopped to move on to SCT and the participant did not progress on anti-CD38 treatment.
  • Are refractory to bortezomib or carfilzomib at the last exposure before this study (defined as participants having PD while receiving bortezomib or carfilzomib therapy or within 60 days after ending bortezomib or carfilzomib therapy).
  • Are planning to undergo SCT prior to PD on this study (ie, these participants should not be enrolled in order to reduce disease burden prior to transplant).
  • Are receiving systemic treatment with strong Cytochrome P450 3A4 (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) within 14 days before randomization.
  • Has received autologous SCT within 12 weeks before the date of study treatment.
Show all 12Show fewer
  • With known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note: FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is <50% of predicted normal.
  • Participants with Grade 2 or higher residual toxicities from prior therapy (including Grade 2 or higher peripheral neuropathy or any grade neuropathy with pain; excluding alopecia). This includes recovery from any major surgery. Note: Participants with planned surgical to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
  • Has uncontrolled clinically significant cardiac disease, including myocardial infarction within 6 months before date of study entry or unstable or uncontrolled angina, congestive heart failure, New York Heart Association (NYHA) Class III-IV, uncontrolled cardiac arrhythmia (Grade 2 or higher).
  • With ongoing or active systemic infection requiring intravenous IV medical management ; participants with known human immunodeficiency virus- Ribonucleic acid (HIV-RNA) positivity; participants with hepatitis B virus (HBV) surface antigen or core antibody positivity; and participants with known hepatitis C virus-RNA positivity. Note: Participants who have positive hepatitis B core antibody can be enrolled but must have hepatitis B virus- deoxyribonucleic acid (DNA) negative. Participants who have positive hepatitis C antibody can be enrolled but must have hepatitis C virus-RNA negativity.
  • Note: Participants who are already enrolled at the time of Amendment 02 should have local HBV testing performed as soon as possible for HBV surface antigen, e antigen, core antibody, and DNA. If any of these tests is positive, consult a physician with expertise in managing HBV for guidance regarding stopping daratumumab, starting HBV antiviral therapy, and remaining on study.
  • Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

Trial locations and contacts

28 sites in 6 countries.

28 sites in 6 countries

United States6 sites

  • Pacific Cancer Medical Center

    Anaheim, California, 92801

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Research Medical Center - Kansas City

    Kansas City, Missouri, 64132

  • SCRI - Tennessee Oncology - Nashville - Centennial

    Nashville, Tennessee, 58014

  • SCRI - Florida Cancer Specialists - Panhandle

    Tallahassee, Florida, 32308

Other trials in United States

Czechia5 sites

  • Fakultni Nemocnice Brno

    Brno, 625 00

  • Fakultni Nemocnice Olomouc

    Olomouc, Olomouc Region, 77900

  • Fakultni Nemocnice Ostrava

    Ostrava - Poruba, Severomoravsky KRAJ, 708 52

  • Fakultni Nemocnice Kralovske Vinohrady

    Prague, Prague, 100 34

  • Onkologicka klinika Vseobecna fakultni nemocnice v Praze a 1

    Prague, 128 08

Other trials in Czechia

Netherlands5 sites

  • Vrije Universiteit Medisch Centrum

    Amsterdam, North Holland, 1081 HV

  • Albert Schweitzer Ziekenhuis Dordwijk

    Dordrecht, South Holland, 3300 AK

  • Medisch Centrum Leeuwarden

    Leeuwarden, Provincie Friesland, 8934 AD

  • Erasmus Medisch Centrum

    Rotterdam, South Holland, 3015 CE

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3584 CX

Other trials in Netherlands

Poland5 sites

  • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza

    Brzozów, Podkarpackie Voivodeship, 36-200

  • Samodzielny Publiczny Zaklad Opieki Zdrowotnej Zespol Szpitali Miejskich

    Chorzów, Silesian Voivodeship, 41-500

  • Szpitale Pomorskie Spolka z ograniczona odpowiedzialnoscia

    Gdynia, Pomeranian Voivodeship, 81-519

  • Szpital Uniwersytecki w Krakowie

    Krakow, Lesser Poland Voivodeship, 31-501

  • Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika w Lodzi

    Lodz, Łódź Voivodeship, 93-510

Other trials in Poland

France4 sites

  • Hopital Claude Huriez

    Lille, Hauts-de-France, 59037

  • Hopital Hotel Dieu

    Nantes, Pays de la Loire Region, 44093

  • Hopital Saint-Antoine

    Paris, Île-de-France Region, 75012

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, Auvergne-Rhône-Alpes, 69495

Other trials in France

Greece3 sites

  • Evaggelismos General Hospital

    Athens, Attica, 10676

  • Alexandra General Hospital of Athens

    Athens, Attica, 11528

  • University General Hospital of Patras Panagia I Voithia

    Patras, Peloponnese, 26504

Other trials in Greece

About this study

Official title: A Phase 2, Open-Label Study of Ixazomib+Daratumumab+Dexamethasone (IDd) in Relapsed and/or Refractory Multiple Myeloma (RRMM)

The purpose of this study is to evaluate the percentage of participants with a response of very good partial response (VGPR) or better to IDd treatment.

Read the detailed description

The regimen being tested in this study is the combination of ixazomib, daratumumab, and dexamethasone. This study will look at the efficacy and safety of IDd in people who have RRMM.

The study will enroll approximately 60 Participants. Participants will be assigned to the treatment group:

  • Ixazomib 4.0 mg + Daratumumab 16.0 mg/kg + Dexamethasone 20 mg

All participants will be asked to take Ixazomib on Days 1, 8 and 15 of each 28-day cycle plus Daratumumab on Days 1, 8, 15 and 22 of each 28-day cycle for Cycles 1 and 2, on Days 1 and 15 of each 28-day cycle for Cycles 3 through 6 and on Day 1 of each 28-day cycle for Cycle 7 and beyond plus Dexamethasone orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle.

This multi-center trial will be conducted in the United States, Czech Republic, France, Poland, Greece and the Netherlands. The overall time to participate in this study is approximately 5 years. Participants will make multiple visits to the clinic, and every 12 weeks after PD until death or termination of the study by the sponsor.

Being tested
Ixazomib, Daratumumab, Dexamethasone
Keywords
Drug Therapy, Ixazomib, Daratumumab, 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.

  • IxazomibDrug

    Also called NINLARO

    Ixazomib capsule.

  • DaratumumabDrug

    Daratumumab IV infusion.

  • DexamethasoneDrug

    Dexamethasone tablets.

Study groups in NCT03439293
Study groupRoleWhat they receive
Ixazomib 4 mg + Daratumumab 16 mg/kg + Dexamethasone 20 mgExperimentalIxazomib, 4 mg, capsules, orally, on Days 1, 8 and 15 of each 28-day cycle along with daratumumab, 16 mg/kg, intravenously (IV), on Days 1, 8, 15 and 22 of Cycles 1 and 2, on Days 1 and 15 (every 2 weeks) for Cycles 3 to 6 and on Day 1 (every 4 weeks) for Cycle 7 and beyond along with dexamethasone, 20 mg, tablets, orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day cycle until progressive disease (PD), unacceptable toxicity, or withdrawal of consent, or up to 5 years.
Receives: Drug: Ixazomib; Drug: Daratumumab; Drug: Dexamethasone

What is being measured

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

  1. Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR)

    Response was assessed using International Myeloma Working Group (IMWG) Criteria. VGPR is defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100 milligram (mg) per 24 hours. The percentage of participants were rounded off to the single decimal point.

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Progression-free Survival (PFS)

    PFS is defined as time from date of first dose of drug to date of first documentation of progressive disease (PD) or death from any cause, whichever occurs first. Participant without documentation of PD or death were censored at the date of last response assessment that is stable disease (SD) or better. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder. SD is defined as not meeting criteria for other responses.

    Measured: Up to 5 years

  2. Time to Progression (TTP)

    TTP is defined as the time from the first dose of any study drug treatment to the date of the first documented PD. PD is defined as increase of 25% of lowest response value in one or more of following criteria: serum M-component (absolute increase ≥0.5 g/dl); or urine M-component (absolute increase ≥200 mg/24-hour); difference between involved and uninvolved FLC levels (absolute increase >10 mg/dl); or bone marrow plasma cell percentage (absolute plasma cell percentage ≥10%); development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma; or development of hypercalcemia that can be attributed solely to plasma cell proliferative disorder.

    Measured: Up to 5 years

  3. Overall Survival (OS)

    OS is defined as the time from the date of first dose of any study drug treatment to the date of death. Participant without documentation of death at the time of analysis will be censored at the last visit at which s/he was known to be alive.

    Measured: Up to 5 years

  4. Overall Response Rate (ORR)

    ORR is defined as percentage of participants with complete response (CR), VGPR and partial response (PR). CR: Negative immunofixation of serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow; normal free light chain (FLC) ratio of 0.26-1.65; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein + urine M-protein level <100 mg/24 hours; and PR: >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions. The percentage of participants were rounded off to the single decimal point.

    Measured: Up to 5 years

  5. Time To Response (TTR)

    TTR is defined as the time from first dose of any study drug treatment to the date of first documentation of PR or better. PR is defined as >=50% reduction of serum M protein and reduction in 24-hour urinary M protein by >=90%/to <200 mg/24 hours; In addition, if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; no known evidence of progressive/new bone lesions.

    Measured: Up to 5 years

  6. Duration of Response (DOR)

    DOR is defined as the time from the date of first documentation of PR or better to the date of the first documented PD among participants who responded to the treatment.

    Measured: Up to 5 years

Timeline

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

  1. First posted20 Feb 2018
  2. Study start13 Mar 2018
  3. Primary completion1 Jan 2022
  4. Study completion26 Jun 2023

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
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03439293
Sponsor's protocol ID
C16047
Other IDs
U1111-1202-6022, 2017-003977-32, 2017
Status last verified
Jun 2024
First submitted
14 Feb 2018
Last updated
3 Jul 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement

Publications

  • Delimpasi S, Dimopoulos MA, Straub J, Symeonidis A, Pour L, Hajek R, Touzeau C, Bhanderi VK, Berdeja JG, Pavlicek P, Matous JV, Robak PJ, Suryanarayan K, Miller A, Villarreal M, Cherepanov D, Srimani JK, Yao H, Labotka R, Orlowski RZ. Ixazomib plus daratumumab and dexamethasone: Final analysis of a phase 2 study among patients with relapsed/refractory multiple myeloma. Am J Hematol. 2024 Sep;99(9):1746-1756. doi: 10.1002/ajh.27382. Epub 2024 Jun 10.

    PubMed 38856176

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ixazomib, Daratumumab and Dexamethasone in people with Multiple Myeloma, run by Takeda at 28 sites in 6 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 12 inclusion and 12 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 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Czechia, Netherlands, Poland, France and 1 more country. 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?

Yes. Results are posted in the registry (first posted 8 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Very Good Partial Response (VGPR) or Better (Complete Response + VGPR) (time frame: Up to 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 NCT03439293, 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 3 Jul 2024.

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