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Ixazomib Plus Lenalidomide Plus Dexamethasone for Newly Diagnosed Myeloma Patients

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ClinicalTrials.gov Identifier: NCT03376672
Recruitment Status : Not yet recruiting
First Posted : December 18, 2017
Last Update Posted : December 18, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Ixazomib Drug: Lenalidomide Drug: Dexamethasone Phase 2

Detailed Description:
This Nordic Myeloma Study Group study is phase 2 study for newly diagnosed transplant eligible myeloma patients between 18 - 70 years of age. Patients will have four IRd cycles of 28 day each as induction consisting of ixazomib 4 mg on days 1, 8 and 15 and lenalidomide 25 mg on days 1-21 and dexamethasone 40 mg on days 1, 8, 15 and 22. After autologous stem cell mobilisation and transplantation patients will receive 2 consolidation cycles with the same combination as during induction. This is followed by risk based maintenance so that high-risk patients will have ixazomib plus lenalidomide maintenance and standard-low risk patients lenalidomide alone. The treatment will continue until progression or excess toxicity. The primary endpoint is minimal residual disease < 0.01% assessed by 8-color flow cytometry (EuroFlow) and secondary endpoint is achievement of minimal residual negativity status assessed by 8-color flow cytometry. Other secondary endpoints are safety, improvement of response during maintenance treatment, progression free survival, time to next treatment, quality of life and overall survival.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Phase 2 Study to Assess the Minimal Residual Disease After Ixazomib Plus Lenalidomide Plus Dexamethasone (IRd) Treatment for Newly Diagnosed Transplant Eligible Myeloma Patients
Anticipated Study Start Date : December 15, 2017
Estimated Primary Completion Date : December 31, 2027
Estimated Study Completion Date : December 31, 2027


Arms and Interventions

Arm Intervention/treatment
Experimental: Ixazomib,lenalidomide,dexamethasone
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
All patients will have similar induction and consolidation treatment with the same regimen.
Drug: Lenalidomide
All patients will have similar induction and consolidation treatment with the same regimen.
Drug: Dexamethasone
All patients will have similar induction and consolidation treatment with the same regimen.
Experimental: High risk maintenance arm
Ixazomib capsules 4Mg Oral capsule on days 1, 8, 15, lenalidomide 10 milligram on days 1-21 in 28d cycle
Drug: Ixazomib
All patients will have similar induction and consolidation treatment with the same regimen.
Drug: Lenalidomide
All patients will have similar induction and consolidation treatment with the same regimen.
Experimental: Standard and low risk maintenance arm
Lenalidomide
Drug: Lenalidomide
All patients will have similar induction and consolidation treatment with the same regimen.


Outcome Measures

Primary Outcome Measures :
  1. Flow cytometric assessment < 0.01% [ Time Frame: 48 months ]
    Minimal residual disease by multiparameter flow cytometry (MFC) < 0.01%


Secondary Outcome Measures :
  1. Flow cytometry negativity [ Time Frame: 48 months ]
    Minimal residual disease negativity by MFC


Other Outcome Measures:
  1. Overall survival [ Time Frame: Up to 10 years ]
    Survival time

  2. Progression free survival [ Time Frame: Up to 10 years ]
    Time without progression of myeloma


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Newly diagnosed transplant eligible male or female multiple myeloma patients, 18-70 years of age, who have not received prior treatment for multiple myeloma
  2. Symptomatic and measurable disease diagnosed by standard criteria (International Myeloma Working Group, CRAB criteria)
  3. 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.
  4. 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.

    4. 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.

    6. 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).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
  • Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault estimation of creatinine clearance (CRcl): CRcl (mL/min) = (140 - age) (weight [kg]) / 72 (serum creatinine [mg/dL]); for females, multiply by 0.85 (Cockcroft DW. 1976, Luke DR. 1990).

    7. Patient must be willing and able to adhere to the study protocol visit schedule and other protocol requirements.

    8. Negative pregnancy test at inclusion if applicable

Exclusion Criteria:

  • 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period.

    2. 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.

    6. 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.

    8. 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.

    9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.

    10. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

    11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

    12. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing.

    13. 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.

    14. Patient has Grade 1 polyneuropathy with pain on clinical examination during the screening period.

    15. 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.

    16. 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.

    17. Primary plasma cell leukemia, POEMS syndrome, Waldenström disease, myelodysplastic syndrome or myeloproliferative disease

    18. Systemic AL amyloidosis/primary amyloidosis or myeloma associated amyloidosis.

    19. Allogeneic stem cell transplantation planned

    20. Participants receiving any other investigational agents or received within 60 days

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03376672


Contacts
Contact: Raija H Silvennoinen, MD, PhD +358 50 327 6348 raija.silvennoinen@helsinki.fi
Contact: Hareth Nahi, MD, PhD hareth.nahi@karolinska.se

Locations
Finland
Helsinki University Central Hospital
Helsinki, Finland
Central Finland Central Hospital Not yet recruiting
Jyväskylä, Finland
Contact: Anu Sikiö, MD       anu.sikio@ksshp.fi   
Kainuu Central Hospital
Kajaani, Finland
Kymenlaakso Central Hospital Not yet recruiting
Kotka, Finland
Contact: Anu Räsänen, MD       anu.rasanen@carea.fi   
Kuopio University Hospital Not yet recruiting
Kuopio, Finland
Contact: Anu Partanen, MD       anu.partanen@kuh.fi   
Päijät-Häme Cebtral Hospital
Lahti, Finland
Oulu University Hospital Not yet recruiting
Oulu, Finland
Contact: Marjaana Säily, MD, PhD       marjaana.saily@ppshp.fi   
Tampere University Hospital
Tampere, Finland
Turku University Hospital
Turku, Finland
Lithuania
VIlnius University Hospital
Vilnius, Lithuania
Norway
Forde Central Hospital South
Forde, Norway
Oslo University Hospital
Oslo, Norway
Stavanger University Hospital
Stavanger, Norway
Trondheim University Hospital
Trondheim, Norway
Sweden
Borås University Hospital Not yet recruiting
Borås, Sweden
Contact: Ulf-Henrik Mellqvist, MD         
Göteborg University Hospital Not yet recruiting
Göteborg, Sweden
Contact: Cecilie Blimark, MD         
Halmstad Hospital Region Halland Not yet recruiting
Halmstad, Sweden
Contact: Conny Karlsson, MD         
Linköping University Hospital Not yet recruiting
Linköping, Sweden
Contact: Lucia Ahlberg, MD         
Sunderby Hospital Region Norrbotten Not yet recruiting
Luleå, Sweden
Contact: Birgitta Lauri, MD         
Lund University Hospital
Lund, Sweden
Helsingborg Hospital Skane Not yet recruiting
Skane, Sweden
Contact: Per Axelsson, MD         
Karolinska University Hospital
Stockholm, Sweden
Uddevalla Hospital Not yet recruiting
Uddevalla, Sweden
Contact: Johanna Abelsson, MD         
Uppsala University Hospital Not yet recruiting
Uppsala, Sweden
Contact: Kristina Carlson, MD         
Varberg Hospital Not yet recruiting
Varberg, Sweden
Contact: Mikael Olsson, MD         
Örebro University Hospital Not yet recruiting
Örebro, Sweden
Contact: Olle Linder, MD         
Sponsors and Collaborators
Raija Silvennoinen
Nordic Myeloma Study Group
Celgene
Takeda
Investigators
Principal Investigator: Raija H Silvennoinen, MD, PhD Helsinki University Central Hospital
More Information

Responsible Party: Raija Silvennoinen, Principal Investigator, Helsinki University Central Hospital
ClinicalTrials.gov Identifier: NCT03376672     History of Changes
Other Study ID Numbers: NMSG#23/15
First Posted: December 18, 2017    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Lenalidomide
Ixazomib
Thalidomide
BB 1101
Glycine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists