Study of Oral Ixazomib in Combination With Melphalan and Prednisone in Participants With Newly Diagnosed Multiple Myeloma

NCT ID: NCT01335685

Last Updated: 2018-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-27
• Study Completion Date: 2016-12-29

Brief Summary

The purpose of this phase 1/2, open-label study was to evaluate the effect of oral formulation of Ixazomib when added to standard melphalan and prednisone (MP) treatment. Both phases of the study included participants who had newly diagnosed multiple myeloma and were ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment was indicated.

Detailed Description

The drug tested in this study was called ixazomib (MLN9708). Ixazomib was tested to treat the people with newly diagnosed multiple myeloma requiring systemic treatment who were not eligible for stem cell transplantation. This study determined the safety, tolerability, efficacy, quality of life (QOL), and pharmacokinetics (PK)/pharmacodynamics (PD) of ixazomib.

The study enrolled 61 patients. The study was conducted in 2 parts: 1) phase 1 dose escalation and 2) phase 2 expansion at maximum tolerated dose. Participants were enrolled to receive:

• Ixazomib 3.0 mg, 3.7 mg, 4.0 mg, or 5.5. mg depending on the treatment assignment

This multicenter trial was conducted in the Unites states, Canada, United Kingdom, Spain and Czech Republic. The overall time to participate in this study is 5.5 years. Participants made multiple visits to the clinic and were followed up every 16 weeks after end of treatment until disease progression if stopped treatment before disease progression and then every 16 weeks up to start of next therapy or death whichever occurs first.

Conditions

Multiple Myeloma

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Ixazomib 3.0 mg

Ixazomib 3.0 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle for up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 23 maintenance cycles; overall up to 32 cycles \[34 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm A: Ixazomib 3.7 mg

Ixazomib 3.7 mg, capsules, orally, on Days 1, 4, 8, 11, 22, 25, 29, 32 plus melphalan 9 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1 to 4 in 42-day cycle for up 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 10 maintenance cycles; overall up to 19 cycles \[21 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm B: Ixazomib 3.0 mg

Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 15 maintenance cycles; overall up to 27 cycles \[25 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm B: Ixazomib 4.0 mg

Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15 cycle plus melphalan 6 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 49 maintenance cycles; overall up to 61 cycles \[58 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm B: Ixazomib 5.5 mg

Ixazomib 5.5 mg, capsules, orally, on Days 1, 8, 15 plus melphalan 6 mg/m\^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1-4 in 28-day cycle for up to 13 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 24 cycles \[24 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm C: Ixazomib 3.0 mg

Ixazomib 3.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m\^2, tablets orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 30 maintenance cycles; overall up to 39 cycles \[40 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm C: Ixazomib 4.0 mg

Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 15, 22, and 29 plus melphalan 9 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 12 maintenance cycles; overall up to 21 cycles \[24 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Arm D: Ixazomib 4.0 mg

Ixazomib 4.0 mg, capsules, orally, on Days 1, 8, 22, and 29 plus melphalan 9 mg/m\^2, tablets, orally on Days 1 to 4 and prednisone 60 mg/m\^2, tablets, orally, on Days 1 to 4 in 42-day cycle for up to 9 cycles in induction phase followed by ixazomib at dose last tolerated in induction, orally, on Days 1, 8, 15 in 28-day cycle up to 12 cycles or until disease progression or unacceptable toxicity if deriving benefit in maintenance phase (up to 28 maintenance cycles; overall up to 37 cycles \[38 months\]).

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Melphalan

Intervention Type: DRUG

Melphalan tablets

Prednisone

Intervention Type: DRUG

Prednisone tablets

Interventions

Ixazomib

Ixazomib capsules

Intervention Type: DRUG

Melphalan

Melphalan tablets

Intervention Type: DRUG

Prednisone

Prednisone tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Is indicated with standard melphalan prednisone (MP) treatment and is not a candidate for high-dose therapy plus stem cell transplantation (HDT-SCT) for 1 of the following reasons: the participant is 65 years of age or older OR the participant is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT
• Is diagnosed with symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage according to standard criteria
• Has measurable disease as specified in study protocol
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Has adequate hematologic, liver, and renal function

Exclusion Criteria

• Has peripheral neuropathy that is greater or equal to Grade 2
• Has major surgery or radiotherapy within 14 days before the first dose of study drug
• Has uncontrolled infection requiring systematic antibiotics
• Has diarrhea (> Grade 1)
• Has prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the participantt)
• Has central nervous system involvement
• Has cardiac status as described in protocol
• Has known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
• Has Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Is diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
• Has serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Lebanon, New Hampshire, United States

Morgantown, West Virginia, United States

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Québec, , Canada

Brno, , Czechia

Prague, , Czechia

Badalona, , Spain

Barcelona, , Spain

Donostia / San Sebastian, , Spain

Madrid, , Spain

Salamanca, , Spain

Seville, , Spain

Bournemouth, , United Kingdom

Brighton, , United Kingdom

Cambridge, , United Kingdom

London, , United Kingdom

Nottingham, , United Kingdom

Oxford, , United Kingdom

Uxbridge, , United Kingdom

Countries

United States; Canada; Czechia; Spain; United Kingdom

References

San-Miguel JF, Echeveste Gutierrez MA, Spicka I, Mateos MV, Song K, Craig MD, Blade J, Hajek R, Chen C, Di Bacco A, Estevam J, Gupta N, Byrne C, Lu V, van de Velde H, Lonial S. A phase I/II dose-escalation study investigating all-oral ixazomib-melphalan-prednisone induction followed by single-agent ixazomib maintenance in transplant-ineligible newly diagnosed multiple myeloma. Haematologica. 2018 Sep;103(9):1518-1526. doi: 10.3324/haematol.2017.185991. Epub 2018 Jun 28.

Reference Type: DERIVED

PMID: 29954932 (View on PubMed)

Other Identifiers

2010-023772-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

C16006

Identifier Type: -

Identifier Source: org_study_id