Ixazomib With Cyclophosphamide and Dexamethasone in Patients With Previously Untreated Symptomatic Multiple Myeloma or Light Chain Amyloidosis

NCT01864018 | Completed Phase 1 Results DMC

• 4 other identifiers: MC1382NCI-2013-01042X1600913-000414
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial studies the side effects and the best dose of cyclophosphamide when given together with ixazomib citrate and dexamethasone in treating patients with previously untreated symptomatic multiple myeloma or light chain amyloidosis. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with ixazomib citrate and dexamethasone may be a better treatment for multiple myeloma or light chain amyloidosis.

Conditions

Amyloidosis; Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated (MTD) Dose of Cyclophosphamide With Ixazomib and Dexamethasone (Phase I)

  Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  At 28 days

• Percentage of Patients With Complete Response or Very Good Partial Response (Phase II, Cohort A)

  The percentage of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 48 weeks

• Rate of Complete Response, Very Good Partial Response, or Partial Response (Phase II, Cohort B)

  The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  Up to 48 weeks

• Maximum Tolerated (MTD) Dose of Cyclophosphamide (Phase I)

  Will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least 1/3 of patients, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  At 28 days

Secondary Outcomes (3)

• Number of Patients Experiencing a Grade 3 or Greater Adverse Event at Least Possibly Related to Treatment as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 5 years

• Progression-free Survival (PFS)

  Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

• Survival Time

  Time from registration to death due to any cause, assessed up to 5 years

Other Outcomes (2)

• Pharmacokinetic (PK) Parameters

  Post-dose, 1 and 4 hours on day 1, pre-dose on days 8, 15, and 22, and day 1 of course 2

• Quality of Life, as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity Questionnaire

  Up to 5 years

Study Arms (1)

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

EXPERIMENTAL

INDUCTION THERAPY: Patients receive ixazomib citrate PO on days 1, 8, and 15 and cyclophosphamide PO and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ixazomib citrate PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Dexamethasone DRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, 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, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, Visumetazone

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Pharmacological Study OTHER

Correlative studies

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Questionnaire Administration OTHER

Ancillary studies

Treatment (ixazomib citrate, cyclophosphamide, dexamethasone)

Eligibility Criteria

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

You may qualify if:

• PHASE I ONLY:
• COHORT A: multiple myeloma
• COHORT B: biopsy proven light chain amyloidosis with organ involvement requiring therapy
• Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min
• Absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 75000/mm\^3
• Hemoglobin \>= 8.0 g/dL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
• COHORT B ONLY: alkaline phosphatase =\< 750 U/L
• COHORT B ONLY: N-terminal pro b-type natriuretic peptide (NT-ProBNP) \< 7500 ng/dL
• Prior therapy for the treatment of solitary plasmacytoma is permitted, but \> 14 days should have elapsed from the last day of radiation; NOTE: prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
• 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

You may not qualify if:

• Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma only
• Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma; NOTE: prior corticosteroid use for the treatment of non-malignant disorders is permitted
• Diagnosed or treated for another malignancy =\< 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease; NOTE: 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
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception
• 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, 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
• Peripheral neuropathy \>= grade 3 on clinical examination or grade 2 with pain during the screening period
• Major surgery =\< 14 days prior to study registration
• Systemic treatment with strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, Gingko biloba, St. John?s wort) =\< 14 days prior to registration
• Evidence of current uncontrolled cardiovascular conditions (New York Heart Association \[NYHA\] class III or IV), including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months; Note: prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
• Radiotherapy =\< 14 days prior to registration; NOTE: if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
• Known human immunodeficiency virus (HIV) positive

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Muchtar E, Gertz MA, LaPlant BR, Buadi FK, Leung N, O'Brien P, Bergsagel PL, Fonder A, Hwa YL, Hobbs M, Helgeson DK, Bradt EE, Gonsalves W, Lacy MQ, Kapoor P, Siddiqui M, Larsen JT, Warsame R, Hayman SR, Go RS, Dingli D, Kourelis TV, Dispenzieri A, Rajkumar SV, Kumar SK. Phase 2 trial of ixazomib, cyclophosphamide, and dexamethasone for previously untreated light chain amyloidosis. Blood Adv. 2022 Sep 27;6(18):5429-5435. doi: 10.1182/bloodadvances.2022007781.

  PMID: 35737873 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Amyloidosis; Multiple Myeloma

Interventions

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

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; 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

507-284-2511

Study Officials

• Shaji Kumar, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2013
• First Posted: May 29, 2013
• Study Start: August 20, 2013
• Primary Completion: April 30, 2021
• Study Completion: September 9, 2023
• Last Updated: July 24, 2025
• Results First Posted: September 21, 2022

Record last verified: 2025-07

Locations

US (2)