AmyloidosisPhase 1/2NCT01864018
Ixazomib With Cyclophosphamide and Dexamethasone in Patients With Previously Untreated Symptomatic Multiple Myeloma or Light Chain Amyloidosis
A Phase 1/2 study testing Cyclophosphamide, Dexamethasone and Ixazomib Citrate in people with Amyloidosis and Plasma Cell Myeloma, run by Mayo Clinic at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyloidosis, Plasma Cell Myeloma
- What is being tested?
- Cyclophosphamide, Dexamethasone and Ixazomib Citrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Aug 2013to 9 Sep 2023
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- COHORT B ONLY: serum immunoglobulin free light chain >= 5 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Previously untreated
- Provide informed written consent
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Willing to follow strict birth control measures as suggested by the study
- Female patients: if they are of childbearing potential, agree to one of the following:
- 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 must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)
- 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
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, 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)
- Willing to return to return to enrolling institution for follow-up (during the active monitoring phase of the study)
Who cannot join
- 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
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- 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
- Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- Any serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with the completion of treatment according to this protocol
- Known allergy to any of the study medications, their analogues or excipients in the various formulations
- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing
- Diarrhea > grade 1, based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grading, in the absence of antidiarrheals
- Participation in clinical trials with other investigational agents not included in this trial, =< 30 days prior to registration
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: Phase 1/2 Trial of Ixazomib in Combination With Cyclophosphamide and Dexamethasone in Patients With Previously Untreated Symptomatic Multiple Myeloma or Light Chain Amyloidosis
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose of cyclophosphamide that can be combined with ixazomib citrate (ixazomib) and dexamethasone in patients with previously untreated symptomatic multiple myeloma (MM). (Phase I Cohort A) II. To determine the complete plus very good partial response rate (>= VGPR) of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated symptomatic MM. (Phase II Cohort A) III. To determine the hematologic response rate of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Phase II Cohort B)
SECONDARY OBJECTIVES:
- To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with ixazomib in combination with cyclophosphamide and dexamethasone followed by ixazomib maintenance till progression. (Cohort A) II. To determine the toxicities associated with ixazomib in combination with cyclophosphamide and dexamethasone in patients with previously untreated symptomatic MM. (Cohort A) III. To determine the organ response rate of ixazomib, used in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Cohort B) IV. To determine the progression free survival and overall survival among patients with previously untreated light chain amyloidosis following treatment with ixazomib in combination with cyclophosphamide and dexamethasone followed by Ixazomib maintenance till progression. (Cohort B) V. To determine the toxicities associated with ixazomib in combination with cyclophosphamide and dexamethasone in patients with previously untreated light chain amyloidosis. (Cohort B)
TERTIARY OBJECTIVES:
- To examine the pharmacokinetics of ixazomib when used in combination with cyclophosphamide and dexamethasone. (Cohort A) II. To assess the incidence of neurotoxicity using patient completed questionnaires. (Cohort A)
OUTLINE: This is a phase I, dose-escalation study of cyclophosphamide followed by a phase II study.
INDUCTION THERAPY: Patients receive ixazomib citrate orally (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.
After completion of study treatment, patients are followed up every 3-6 months for 5 years.
- Conditions
- Amyloidosis, Plasma Cell Myeloma
- Being tested
- Cyclophosphamide, Dexamethasone, Ixazomib Citrate, Laboratory Biomarker Analysis, Pharmacological Study
- Medical subject headings
- Amyloidosis, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given PO
DexamethasoneDrug
Also called Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex
Given PO
Ixazomib CitrateDrug
Also called MLN-9708, MLN9708, Ninlaro
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. A grade 3 event is one that is severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL.
Measured: Up to 5 years
Progression-free Survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan Meier.
Measured: 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
The distribution of survival time will be estimated using the method of Kaplan-Meier.
Measured: Time from registration to death due to any cause, assessed up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study start20 Aug 2013
- Primary completion30 Apr 2021
- Study completion9 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shaji Kumar, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864018
- Sponsor's protocol ID
- MC1382
- Other IDs
- NCI-2013-01042, X16009, MC1382, 13-000414
- Status last verified
- Jul 2025
- First submitted
- 23 May 2013
- Last updated
- 24 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35737873