Ixazomib, Cyclophosphamide and Dexamethasone for Multiple Myeloma

NCT02412228 | Completed Phase 2 Results DMC

• 1 other identifier: 299
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Evaluation of the Response Rate of Ixazomib With Metronomic Cyclophosphamide and Dexamethasone for First-line Treatment of Multiple Myeloma.

  Through study treatment completion, an average of 2 years

Secondary Outcomes (1)

• Evaluation of the Toxicities Associated With Ixazomib With Metronomic Cyclophosphamide and Dexamethasone.

  Assessed at baseline and end of study, up to 2 years, end of study reported

Study Arms (1)

Ixazomib Regimen

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

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

Also known as: MLN978

Ixazomib Regimen

Cyclophosphamide DRUG

Cycle 1: Cyclophosphamide: 50 mg/day continuous daily Cycles 2-6: Cyclophosphamide: 50 mg/day continuous daily

Also known as: cytophosphane

Ixazomib Regimen

Dexamethasone DRUG

Cycle 1: Dexamethasone: 20 mg/day 1, 8, 15 Cycles 2-6: Dexamethasone: 20 mg/day 1, 4, 8, 11, 15, 18

Also known as: Ozurdex

Ixazomib Regimen

Eligibility Criteria

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

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• John L. Reagan: lead
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator
• Memorial Hospital of Rhode Island: collaborator

Study Sites (3)

Memorial Hospital of Rhode Island

Pawtucket, Rhode Island, 02860, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Related Publications (1)

• Pelcovits A, Barth P, Reagan JL, Olszewski AJ, Rosati V, Wood R, Sturtevant A, Winer ES. Ixazomib, Oral Metronomic Cyclophosphamide, and Dexamethasone for First-Line Treatment of Multiple Myeloma: A Phase II Brown University Oncology Group Study. Oncologist. 2023 May 8;28(5):462-e303. doi: 10.1093/oncolo/oyad017.

  PMID: 36942937 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Cyclophosphamide; Dexamethasone; Calcium Dobesilate

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: John Reagan, MD
• Organization: Brown University Oncology Research Group

BrUOG@Brown.edu

401-863-3000

Study Officials

• Howard Safran, MD

  BrUOG

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator: Sponsor-Investigator

Study Record Dates

• First Submitted: February 16, 2015
• First Posted: April 9, 2015
• Study Start: August 1, 2015
• Primary Completion: March 29, 2019
• Study Completion: November 9, 2023
• Last Updated: October 15, 2025
• Results First Posted: May 21, 2021

Record last verified: 2025-10

Locations

US (3)