Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients

NCT03376672 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NMSG#23/15
• Study Type: interventional
• Target: 120
• Locations: 4 countries
• Sites: 26

Brief Summary

This study will evaluate the efficacy and safety of 3-drug all-oral combination, ixazomib plus lenalidomide plus dexamethasone (IRd) as induction treatment for autologous stem cell transplantation eligible patients followed by IRd consolidation and risk based maintenance treatment with IR or R alone.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Flow cytometric assessment < 0.01%

  Minimal residual disease by multiparameter flow cytometry (MFC) \< 0.01%

  48 months

Secondary Outcomes (1)

• Flow cytometry negativity

  48 months

Other Outcomes (2)

• Overall survival

  Up to 10 years

• Progression free survival

  Up to 10 years

Study Arms (3)

Ixazomib,lenalidomide,dexamethasone

EXPERIMENTAL

Ixazomib capsules 4Mg Oral capsule on days 1, 8 and 15 in 28d cycle, lenalidomide 25 milligram capsules on days 1-21 in 28d cycle, dexamethasone 40 milligram capsules on days 1, 8, 15, 22 in 28d cycle

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

High risk maintenance arm

EXPERIMENTAL

Ixazomib capsules 4Mg Oral capsule on days 1, 8, 15, lenalidomide 10 milligram on days 1-21 in 28d cycle

Drug: Ixazomib; Drug: Lenalidomide

Standard and low risk maintenance arm

EXPERIMENTAL

Lenalidomide

Drug: Lenalidomide

Interventions

Ixazomib DRUG

All patients will have similar induction and consolidation treatment with the same regimen.

High risk maintenance arm; Ixazomib,lenalidomide,dexamethasone

Lenalidomide DRUG

All patients will have similar induction and consolidation treatment with the same regimen.

High risk maintenance arm; Ixazomib,lenalidomide,dexamethasone; Standard and low risk maintenance arm

Dexamethasone DRUG

All patients will have similar induction and consolidation treatment with the same regimen.

Ixazomib,lenalidomide,dexamethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed transplant eligible male or female multiple myeloma patients, 18-70 years of age, who have not received prior treatment for multiple myeloma
• Symptomatic and measurable disease diagnosed by standard criteria (International Myeloma Working Group, CRAB criteria)
• Voluntary written informed consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, fertile, agree to practice 2 effective methods of contraception, at the same time, and agree to ongoing pregnancy testing and adhere to the guidelines of the lenalidomide pregnancy prevention program from the time of signing the informed consent form 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 \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.)
• Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
• Agree to practice effective barrier contraception and adhere to the guidelines of the lenalidomide pregnancy prevention program 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 (eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.
• \. Patients must have a diagnosis of a symptomatic multiple myeloma without any previous therapies except dexamethasone 160 mg dose, or comparable dose of other steroids, and local radiotherapy for symptom control 5. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
• \. Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1,000/mm3 (≥ 1.0 x 109/L) and platelet count ≥ 75,000/mm3 (75 x 109/L). Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
• Total bilirubin ≤ 1.5 × the upper limit of the normal range (ULN).

You may not qualify if:

• \. Female patients who are lactating or have a positive serum pregnancy test during the screening period.
• \. Major surgery within 14 days before enrollment. 3. Radiotherapy within 14 days before enrollment 4. Central nervous system involvement with multiple myeloma. 5. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
• \. Inability, unwillingness or contraindication to use thrombosis prophylaxis or antithrombotic therapy or herpes zoster prophylaxis 7. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• \. Systemic treatment, within 14 days before the first dose of ixazomib, 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 or lenalidomide including difficulty swallowing.
• \. Diagnosed or treated for another malignancy within 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• \. Patient has Grade 1 polyneuropathy with pain on clinical examination during the screening period.
• \. 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.
• \. Patients that have previously been treated for multiple myeloma or smoldering myeloma with ixazomib or any other therapy, or participated in a study with ixazomib whether treated with ixazomib or not.
• \. Primary plasma cell leukemia, POEMS syndrome, Waldenström disease, myelodysplastic syndrome or myeloproliferative disease
• \. Systemic AL amyloidosis/primary amyloidosis or myeloma associated amyloidosis.
• \. Allogeneic stem cell transplantation planned

Sponsors & Collaborators

• Raija Silvennoinen: lead
• Nordic Myeloma Study Group: collaborator
• Celgene: collaborator
• Takeda: collaborator

Study Sites (26)

Helsinki University Central Hospital

Helsinki, Finland

Location

Central Finland Central Hospital

Jyväskylä, Finland

Location

Kainuu Central Hospital

Kajaani, Finland

Location

Kymenlaakso Central Hospital

Kotka, Finland

Location

Kuopio University Hospital

Kuopio, Finland

Location

Päijät-Häme Central Hospital

Lahti, Finland

Location

Oulu University Hospital

Oulu, Finland

Location

Tampere University Hospital

Tampere, Finland

Location

Turku University Hospital

Turku, Finland

Location

VIlnius University Hospital

Vilnius, Lithuania

Location

Forde Central Hospital South

Førde, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

Trondheim University Hospital

Trondheim, Norway

Location

Borås University Hospital

Borås, Sweden

Location

Göteborg University Hospital

Gothenburg, Sweden

Location

Halmstad Hospital Region Halland

Halmstad, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Sunderby Hospital Region Norrbotten

Luleå, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Helsingborg Hospital Skane

Skåne, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Uddevalla Hospital

Uddevalla, Sweden

Location

Uppsala University Hospital

Uppsala, Sweden

Location

Varberg Hospital

Varberg, Sweden

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Raija H Silvennoinen, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2017
• First Posted: December 18, 2017
• Study Start: May 31, 2018
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (4); FI (9); LI (1); SE (12)