Ixazomib, Cyclophosphamide and Dexamethasone for Multiple Myeloma

October 6, 2025 updated by: John L. Reagan

BrUOG 299: Ixazomib, Oral Metronomic Cyclophosphamide and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study.

The goal of this proposal is to develop a more effective and better tolerated regimen. Ixazomib appears to have greater activity than bortezomib with less peripheral neuropathy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

1.1 PRIMARY OBJECTIVE: 1.1.1 To evaluate the response rate of Ixazomib with metronomic cyclophosphamide and dexamethasone for first-line treatment of multiple myeloma 1.2 SECONDARY OBJECTIVES: 1.2.1To evaluate the toxicities associated with Ixazomib with metronomic cyclophosphamide and dexamethasone.

1.2.2 Estimate the progression-free survival and overall survival of Ixazomib with metronomic cyclophosphamide and dexamethasone for first-line treatment of multiple myeloma

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Rhode Island
      • Pawtucket, Rhode Island, United States, 02860
        • Memorial Hospital of Rhode Island
      • Providence, Rhode Island, United States, 02906
        • The Miriam Hospital
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years of age
  • Histologically confirmed multiple myeloma according to WHO classification. Pathology report to be sent to BrUOG for confirmation
  • Diagnosis of Multiple Myeloma that has not been previously treated (although patients that received emergent steroid and/or local radiation therapy will be permitted to enter the study). , Details need to be submitted to BrUOG with dates and doses.
  • Measureable disease defined as either an elevated serum M-protein, urine M-protein, bone marrow involvement >30% or serum free light chains per the IMWG criteria. Confirmation to be sent to BrUOG, see section 7 for criteria
  • Life expectancy of ≥ 6 months, confirmation per treating investigator required
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. If transfusional support provided, please document for submission to BrUOG
  • Calculated creatinine clearance ≥30 mL/min (based on the Cockcroft-Gault Equation below)

For males:

Creatinine Clearance = (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

For females:

Creatinine Clearance = 0.85 (140-age[years] x weight [kg]) 72 x (serum creatinine[mg/dL])

  • ECOG performance status of 0-1.
  • Adequate Liver function; AST or ALT < 3.0 x upper limit of normal (ULN); Total bilirubin <1.5x ULN
  • Voluntary written 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, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug and obtain a pregnancy test, which must come back negative prior to drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject and obtain a serum pregnancy test, which must come back negative prior to drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG. Female's menopausal status to be documented and submitted to BrUOG if applicable. Pregnancy test, if applicable, required to be sent to BrUOG.

  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception 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.) Documentation and confirmation of conversations and patient commitment to contraception is required to be noted and sent to BrUOG.

Exclusion Criteria:

  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Any surgery within 14 days before enrollment.
  • Radiotherapy within 14 days before enrollment.
  • Central nervous system involvement (myeloma-related).
  • Active infection requiring systemic antibiotic therapy or other serious active infection within 7 days before study enrollment.
  • 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, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or 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. If not applicable, then investigator to document not applicable
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. If not applicable, then investigator to document not applicable
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. If not applicable, then investigator to document not applicable
  • Diagnosed or treated for another malignancy within 2 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 2 peripheral neuropathy or Grade 1 with pain.
  • Participation in other therapeutic 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ixazomib Regimen

Cycle 1: Ixazomib: 4mg/day 1, 8, 15, Cyclophosphamide: 50 mg/day continuous daily, Dexamethasone: 20 mg/day 1, 8, 15 Cycles 2-6: Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18, Cyclophosphamide: 50 mg/day continuous, daily, Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18

Maintenance:

Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years
Drug: Ixazomib

Cycle 1:

Ixazomib: 4mg/day 1, 8, 15

Cycles 2-6:

Ixazomib: 4mg/day 1, 4, 8, 11, 15, 18,

Maintenance:

Ixazomib at 4 mg days 1, 8 and 15 of a 28 day cycle for 1 ½ years

Other Names:
  • MLN978
Drug: Cyclophosphamide

Cycle 1:

Cyclophosphamide: 50 mg/day continuous daily

Cycles 2-6:

Cyclophosphamide: 50 mg/day continuous daily

Other Names:
  • cytophosphane
Drug: Dexamethasone

Cycle 1:

Dexamethasone: 20 mg/day 1, 8, 15

Cycles 2-6:

Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18

Other Names:
  • Ozurdex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma.
Time Frame: Through study treatment completion, an average of 2 years
Through study treatment completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone.
Time Frame: Assessed at baseline and end of study, up to 2 years, end of study reported
Assessed at baseline and end of study, up to 2 years, end of study reported

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

John L. Reagan

Collaborators

The Miriam Hospital
Rhode Island Hospital
Memorial Hospital of Rhode Island

Investigators

  • Study Chair: Howard Safran, MD, BrUOG

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

March 29, 2019

Study Completion (Actual)

November 9, 2023

Study Registration Dates

First Submitted

February 16, 2015

First Submitted That Met QC Criteria

April 5, 2015

First Posted (Estimated)

April 9, 2015

Study Record Updates

Last Update Posted (Estimated)

October 15, 2025

Last Update Submitted That Met QC Criteria

October 6, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 299

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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