Ixazomib Citrate in Treating Patients With Relapsed Multiple Myeloma That Is Not Refractory to Bortezomib

NCT01415882 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC1181NCI-2011-0230311-001516
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well ixazomib citrate works in treating patients with multiple myeloma that has returned after a period of improvement (relapsed) but is not resistant to bortezomib (refractory). Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

• Proportion of Confirmed Responses With Ixazomib Citrate Alone (Arm A [Closed]), Ixazomib Citrate With Dexamethasone (Arms B + C), or With Dexamethasone and Cyclophosphamide (Arm D), or With Dexamethasone, Cyclophosphamide, Daratumumab (Arm E)

  A confirmed response is defined as stringent complete response, complete response (CR), very good partial response, or partial response (PR) noted as the objective status on 2 separate evaluations while receiving ixazomib citrate with or without dexamethasone. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. 95% confidence intervals for the true success proportion will be calculated by the exact binomial method.

  2.5 years

Secondary Outcomes (4)

• Confirmed Response Rate With the Addition of Dexamethasone (Arm A Only)

  2.5 years

• Overall Survival

  2.5 years

• Event-free Survival

  From registration to disease progression while receiving ixazomib citrate and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma, assessed up to 2.5 years

• Incidence of Adverse Events

  Up to 30 days after the last day of study drug treatment

Study Arms (5)

Arm A (ixazomib citrate and dexamethasone, closed to accrual)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15. Patients with lack of minor response by the end of the second cycle or lack of partial response by the end of the fourth cycle also receive dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis

Arm B (ixazomib citrate and dexamethasone)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15 and dexamethasone PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis

Arm C (higher-dose ixazomib citrate and dexamethasone)

EXPERIMENTAL

Patients receive higher doses of ixazomib citrate PO on days 1, 8, and 15 and dexamethasone PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis

Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15 and cyclophosphamide PO (cycles 1-18 only) and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis

Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

EXPERIMENTAL

Patients receive ixazomib citrate PO on days 1, 8, and 15, cyclophosphamide PO (cycles 1-12 only) on days 1, 8, 15, 22, and daratumumab IV on days 1, 8, 15, 22 (cycles 1-2), days 1 and 15 (cycles 3-6), and day 1 in all subsequent cycles. Patients also receive dexamethasone IV or PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Biological: Daratumumab; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis

Interventions

Cyclophosphamide DRUG

Given PO

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide); Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

Dexamethasone DRUG

Given PO or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (ixazomib citrate and dexamethasone, closed to accrual); Arm B (ixazomib citrate and dexamethasone); Arm C (higher-dose ixazomib citrate and dexamethasone); Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide); Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Arm A (ixazomib citrate and dexamethasone, closed to accrual); Arm B (ixazomib citrate and dexamethasone); Arm C (higher-dose ixazomib citrate and dexamethasone); Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide); Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (ixazomib citrate and dexamethasone, closed to accrual); Arm B (ixazomib citrate and dexamethasone); Arm C (higher-dose ixazomib citrate and dexamethasone); Arm D (ixazomib citrate, dexamethasone, and cyclophosphamide); Arm E (ixazomib citrate, cyclophosphamide, daratumumab)

Eligibility Criteria

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

You may qualify if:

• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min (obtained =\< 14 days prior to registration)
• Absolute neutrophil count \>= 1000/mL (obtained =\< 14 days prior to registration)
• Untransfused platelet count \>= 75000/mL (obtained =\< 14 days prior to registration)
• Hemoglobin \>= 8.0 g/dL (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (obtained =\< 14 days prior to registration)
• Patients with relapsed multiple myeloma who have already received one or more standard treatment regimens
• Measurable disease of multiple myeloma as defined by at least ONE of the following:
• Serum monoclonal protein \>= 1.0 g/dL
• \>= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
• Serum immunoglobulin free light chain \>= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
• For patients with extramedullary disease (EMD) measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) or the CT portion of the positron emission tomography (PET)/CT: Must have at least one lesion that has a single diameter of \>= 2 cm. Skin lesions can be used if the area is \>= 2 cm in at least one diameter and measured with a ruler
• Plasma cell count \>= 0.5 x 10\^9/L or 5 percent of the peripheral blood white cells
• Plasma cell count if determined by flow cytometry, \>= 200/150,000 events
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2

You may not qualify if:

• Recent prior chemotherapy:
• Alkylators (e.g. melphalan, cyclophosphamide) =\< 14 days prior to registration
• Anthracyclines =\< 14 days prior to registration
• High dose corticosteroids, immune modulatory drugs (thalidomide or lenalidomide) =\< 7 days prior to registration
• Prior therapy with any proteasome inhibitor other than bortezomib, carfilzomib, or ixazomib
• Concomitant high dose corticosteroids other than what is part of treatment protocol (concurrent use of corticosteroids); EXCEPTION: patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
• 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
• Any of the following:
• Pregnant women or women of reproductive ability who are unwilling to use 2 effective methods of contraception from the time of signing the informed consent form through 90 days after the last dose of study drug
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 30 days after stopping treatment
• Other co-morbidity which would interfere with patient's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• Patient has \>= grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination during the screening period
• Major surgery within 14 days before study registration

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Kumar SK, LaPlant BR, Reeder CB, Roy V, Halvorson AE, Buadi F, Gertz MA, Bergsagel PL, Dispenzieri A, Thompson MA, Crawley J, Kapoor P, Mikhael J, Stewart K, Hayman SR, Hwa YL, Gonsalves W, Witzig TE, Ailawadhi S, Dingli D, Go RS, Lin Y, Rivera CE, Rajkumar SV, Lacy MQ. Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. Blood. 2016 Nov 17;128(20):2415-2422. doi: 10.1182/blood-2016-05-717769. Epub 2016 Oct 4.

  PMID: 27702799 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; daratumumab; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; ixazomib

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: Shaji Kumar
• Organization: Mayo Clinic

Kumar.Shaji@mayo.edu

507-284-5096

Study Officials

• Shaji K. Kumar, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2011
• First Posted: August 12, 2011
• Study Start: January 31, 2012
• Primary Completion: April 21, 2023
• Study Completion: April 30, 2025
• Last Updated: September 5, 2025
• Results First Posted: June 13, 2024

Record last verified: 2025-08

Locations

US (3)