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Multiple MyelomaPhase 2DARIANCT03746652

Safety and Efficacy of Daratumumab in Combination With Ixazomib and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

A Phase 2 study testing Daratumumab, Ixazomib, Dexamethasone in people with Multiple Myeloma, run by Hellenic Society of Hematology at 1 site in Greece.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study will assess the efficacy of daratumumab in combination with ixazomib and dexamethasone as second line treatment for relapsed Multiple Myeloma patients. 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?
Daratumumab, Ixazomib, Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteGreece
Study dates
Dec 2018to Dec 2021
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

  • Males and females at least 18 years of age.
  • Voluntary written informed consent before performance of any study-related procedure.
  • Relapsed patients with measurable disease parameters according to the IMWG:
  • IgG multiple myeloma: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours, or
  • IgA, IgD, IgE, IgM multiple myeloma: Serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or
  • Light chain multiple myeloma, for patients without measurable disease in the serum or urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
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  • Patients who have received one prior regimen for MM based on lenalidomide (induction followed by any planned high dose therapy or consolidation or maintenance would be considered as one regimen).
  • Patients must have documented evidence of PD based on the investigator's determination of response as defined by the modified IMWG criteria.
  • Willingness and ability to participate in study procedures.
  • Patient has a Karnofsky Performance Status ≥ 70.
  • For patients experiencing toxicities resulting from previous therapy, the toxicities must be resolved or stabilized to ≤ Grade 1.
  • Patients with adequate bone marrow reserve, as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1.0×10^9/L.
  • Platelet count ≥ 75×10^9/L for patients in whom < 50% of bone marrow nucleated cells are plasma cells and ≥ 50×10^9/L for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted to reach this level).
  • All of the following results during Screening:
  • Hemoglobin level ≥8 g/dL (≥ 4.65 mmol/L) (transfusions are not permitted to reach this level).
  • Creatinine clearance ≥30 mL/min by CKD-EPI.
  • Alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN).
  • Aspartate aminotransferase (AST) level ≤ 2.5×ULN.
  • Total bilirubin level ≤ 1.5×ULN, (except for Gilbert Syndrome: direct bilirubin ≤1.5×ULN).
  • Serum calcium corrected for albumin ≤ 14.0 mg/dL (≤ 3.5 mmol/L), or free ionized calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L).

Who cannot join

  • Previous exposure to anti-CD38 antibodies or ixazomib.
  • Systemic treatment with or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort within 14 days before C1D1.
  • Patient has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, prior to C1D1. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days) for palliative treatment before C1D1.
  • Previous allogenic stem cell transplant; or autologous stem cell transplantation (ASCT) within 12 weeks before C1D1.
  • Patient has received radiotherapy within 14 days of C1D1. Urgent localized radiotherapy for Spinal Cord Compression is allowed.
  • History of malignancy (other than MM) within 3 years before C1D1 (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other noninvasive lesion that in the opinion of the investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
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  • Clinical signs of meningeal involvement of MM.
  • Patient has clinically significant cardiac disease, including: unstable angina or myocardial infarction within 6 months to C1D1, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless patient has a pacemaker, or ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) > 470 msec.
  • Known active hepatitis A, B, or C.
  • Known HIV infection.
  • Patient has a history of significant neurological, endocrine, gastrointestinal, respiratory, or inflammatory illness or stroke; or COPD requiring > 2 hospitalizations in the preceding 12 months from C1D1.
  • Patient has plasma cell leukemia (> 2.0×10^9/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
  • Patient has uncontrolled hypertension or hypertension requiring >2 medications for adequate control within 14 days to C1D1.
  • Patient has uncontrolled diabetes within 14 days to C1D1 or diabetes mellitus with > 2 episodes of ketoacidosis in the preceding 12 months from C1D1.
  • Patient has ongoing ≥ Grade 2 peripheral neuropathy.
  • Patient had ≥ Grade 3 rash during prior therapy.
  • Patient has had major surgery within 14 days prior to C1D1, or has not fully recovered from an earlier surgery, or has surgery planned during the time the patient is expected to participate in the study or within 2 weeks after the last dose of study drug administration. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery.
  • Pregnant or nursing women.
  • Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence.
  • 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.
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
  • 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.

Trial locations and contacts

1 site in 1 country.

Panayiotis Panayiotidis, Prof. contact

+302107211806

infohaema@eae.gr

Greece1 site

  • General Hospital of Athens "Alexandra"

    Athens, Attica, 11528

    Evangelos Terpos, Prof., +302103381512

Other trials in Greece

About this study

Official title: A Phase 2, Multicenter, Open-label, Single-Arm Study to Evaluate the Safety and Efficacy of Daratumumab in Combination With Ixazomib and Dexamethasone as Second Line Therapy in Multiple Myeloma Patients Who Have Received Prior Treatment With a Lenalidomide Based Regimen

This study will assess the efficacy of daratumumab in combination with ixazomib and dexamethasone as second line treatment for relapsed Multiple Myeloma patients.

Read the detailed description

This is a Phase 2, single-arm study of daratumumab in combination with ixazomib and dexamethasone as second line treatment for relapsed Multiple Myeloma patients initially treated with lenalidomide-based regimens. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on CD38, a transmembrane glycoprotein. It is a targeted immunotherapy that attacks tumor cells that overexpress CD38, in a variety of hematological malignancies including multiple myeloma. Ixazomib is an orally administered proteasome inhibitor with anti-myeloma activity.

Being tested
Daratumumab, Ixazomib, Dexamethasone
Keywords
Second line treatment; Daratumumab; Ixazomib; 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.

  • Daratumumab, Ixazomib, DexamethasoneDrug

    Daratumumab 16 mg/kg, Ixazomib 4 mg, Dexamethasone 40 mg

Study groups in NCT03746652
Study groupRoleWhat they receive
DIdExperimentalDaratumumab, Ixazomib, Dexamethasone
Receives: Drug: Daratumumab, Ixazomib, Dexamethasone

What is being measured

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

  1. Overall Response Rate (ORR)

    ORR is defined as the proportion of patients who achieve a best response of PR or better, using modified IMWG criteria.

    Measured: From first day of treatment until end of study, documented progressive disease (PD), or death (approximately up to 36 months)

Secondary outcomes (8)

  1. Evaluation of the hematologic and non-hematologic toxicity profile of the combination.

    Toxicities related to the administration of Daratumumab or Ixazomib will be assessed (e.g., neutropenia, thrombocytopenia, nausea, peripheral neuropathy, rash, etc.).

    Measured: From first day of treatment until end of study, PD, or death (approximately up to 36 months)

  2. Duration of response (DOR)

    For patients who have not progressed, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy.

    Measured: From the date of initial documentation of a response (CR, VGPR or PR) to the date of first documented evidence of PD, as defined in the IMWG criteria (approximately up to 36 months)

  3. Time to disease progression (TTP)

    Time in months from first dose of treatment until PD.

    Measured: From C1D1 to the date of first documented evidence of PD, as defined in the IMWG criteria (approximately up to 36 months)

  4. Progression-free survival (PFS)

    For patients who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to be PD and is not included in the PFS calculation.

    Measured: From C1D1 to either PD, according to the IMWG criteria, or death, whichever occurs first (approximately up to 36 months)

  5. Overall survival (OS)

    Overall survival (OS) is measured from C1D1 to the date of the patient's death. If the patient is alive or the vital status is unknown at the time of the analysis, then the patient's data will be censored at the date the patient was last known to be alive.

    Measured: From C1D1 to the date of death from any cause (approximately up to 36 months)

  6. Time to next therapy (TNT)

    For patients who neither start a new anti-neoplastic therapy nor die, survival time will be censored at the date of their last available follow-up date. For a patient who does not have any post-baseline follow-up assessments and who has not died, survival time will be censored at C1D1.

    Measured: From C1D1 to the date of the next anti-neoplastic therapy or death from any cause, whichever comes first (approximately up to 36 months)

  7. Minimal Residual Disease (MRD) negativity using Next-Generation Flow Cytometry (NGFC)

    MRD negativity rate is defined as the proportion of patients who achieve a negative result of MRD. Patients without MRD assessment will be considered as having MRD-positive results.

    Measured: Assessed every 3 months post CR/sCR until PD (approximately up to 36 months)

  8. Serum bone markers

    NTX, CTX, bALP, RANKL, OPG, Dkk-1, SOST and serum angiogenic cytokines levels angiogenin, VEGF, angiopoietin-1 and -2.

    Measured: The evaluation will be performed on C1D1 and then every 3 months until PD (approximately up to 36 months)

Timeline

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

  1. First posted20 Nov 2018
  2. Study startDec 2018 (estimated)
  3. Primary completionDec 2021 (estimated)
  4. Study completionDec 2021 (estimated)

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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03746652
Sponsor's protocol ID
ΕΑΕ-2018/ΜΜ03
Acronym
DARIA
Status last verified
Nov 2018
First submitted
13 Nov 2018
Last updated
23 Nov 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Ixazomib, Dexamethasone in people with Multiple Myeloma, run by Hellenic Society of Hematology at 1 site in Greece.

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 21 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 23 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Greece. 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?

Results are not available in the source record.

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

Contact Panayiotis Panayiotidis, Prof. (+302107211806, infohaema@eae.gr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: From first day of treatment until end of study, documented progressive disease (PD), or death (approximately up to 36 months)). 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 NCT03746652.

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 23 Nov 2018.

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