NCT03012880 · REGISTRY CONDITION SEARCH

Ixazomib Citrate, Lenalidomide, Dexamethasone, and Daratumumab in Treating Patients With Newly Diagnosed Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-06-04

This phase II trial studies how well ixazomib citrate, lenalidomide, dexamethasone, and daratumumab work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide 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. Monoclonal antibodies, such as daratumumab, may block cancer growth in different ways by targeting certain cells. Giving ixazomib citrate, lenalidomide, dexamethasone, and daratumumab may work better in treating patients with newly diagnosed multiple myeloma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Proportion of Patients Who Achieve a Confirmed Complete Response (CR)

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outcome · POSTED

Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Progression Free Survival

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outcome · POSTED

Rate of >= Very Good Partial Response (VGPR)

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outcome · NOT POSTED

Minor Response Development (MRD)

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outcome · NOT POSTED

Neurotoxicity

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Calculated creatinine clearance (using Cockcroft-Gault equation) \>= 30 mL/min * Absolute neutrophil count (ANC) \>= 1500/mm\^3 * Untransfused 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) =\< 2.5 x ULN * 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 * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * Previously untreated for myeloma or have received no more than one cycle of any treatment regimen; NOTE: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted; 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 * 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 * 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 \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) * Male patients: even if surgically sterilized (i.e., 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 enrolling institution for follow-up (during the active monitoring phase of the study) * Willing to follow the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program * Willing to provide bone marrow and blood samples for planned research Exclusion Criteria: * Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma * Diagnosed or treated for another malignancy =\< 2 years prior to registration 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 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 2 on clinical examination or grade 1 with pain during the screening period * Major surgery =\< 14 days prior to registration * Systemic treatment with strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's wort) =\< 14 days prior to registration * Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction =\< 6 months; Note: Prior to entry, any 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 allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure), or known sensitivity to mammalian-derived products * Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib, lenalidomide or dexamethasone 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
INDUCTION PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab IV over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity.
intervention Names
Biological: Daratumumab
Drug: Dexamethasone
Drug: Ixazomib Citrate
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Other: Questionnaire Administration
label
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Given IV
name
Daratumumab
other Names
Anti-CD38 Monoclonal Antibody
Darzalex
HuMax-CD38
JNJ-54767414
type
BIOLOGICAL
arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Given PO
name
Dexamethasone
other Names
Aacidexam
Adexone
Aknichthol Dexa
Alba-Dex
Alin
Alin Depot
Alin Oftalmico
Amplidermis
Anemul mono
Auricularum
Auxiloson
Baycuten
type
DRUG
arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Given PO
name
Ixazomib Citrate
other Names
MLN-9708
MLN9708
Ninlaro
type
DRUG
arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Given PO
name
Lenalidomide
other Names
CC-5013
CC5013
CDC 501
Revlimid
type
DRUG
arm Group Labels
Treatment (ixazomib, lenalidomide, daratumumab, dexamethasone)
description
Ancillary studies
name
Questionnaire Administration
type
OTHER

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 80
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Will be assessed on bone marrow aspirate in all patients achieving CR. The proportion of patients who achieve MRD negative status will be estimated by the number of patients who are MRD negative divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.
measure
Minor Response Development (MRD)
time Frame
Up to 2 years
description
The FACT/GOG neurotoxicity questionnaire will be completed. Patients will be evaluated by overall score for each questionnaire at each time point and changes over time will be calculated. These measures will be correlated with outcome using Fisher's exact test and Kaplan-Meier methods where appropriate.
measure
Neurotoxicity
time Frame
Baseline up to 2 years

primary Outcomes

measure
Proportion of Patients Who Achieve a Confirmed Complete Response (CR)
time Frame
2 years

secondary Outcomes

description
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables are in the adverse event section of this report. The rate of patients that suffered a grade 3 or higher adverse event are reported here.
measure
Proportion of Patients That Experienced a Grade 3 or Higher Adverse Event.
time Frame
2 years
description
Will be estimated by the number of patients who achieve a stringent complete response (sCR), CR, VGPR or partial response (PR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
measure
Overall Response Rate (ORR)
time Frame
2 years
description
The distribution of overall survival will be estimated using the method of Kaplan-Meier.
measure
Overall Survival (OS)
time Frame
2 years
description
The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
measure
Progression Free Survival
time Frame
2 years
description
Will be estimated by the number of patients with a VGPR, CR, or Stringent Complete Response (sCR) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportions will be calculated.
measure
Rate of >= Very Good Partial Response (VGPR)
time Frame
2 years

Full study description

brief Summary: This phase II trial studies how well ixazomib citrate, lenalidomide, dexamethasone, and daratumumab work in treating patients with newly diagnosed multiple myeloma. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide 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. Monoclonal antibodies, such as daratumumab, may block cancer growth in different ways by targeting certain cells. Giving ixazomib citrate, lenalidomide, dexamethasone, and daratumumab may work better in treating patients with newly diagnosed multiple myeloma.
detailed Description: PRIMARY OBJECTIVES: I. To determine the complete response rate (CR) of the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic multiple myeloma (MM). SECONDARY OBJECTIVES: I. To determine the overall response rate (ORR), and very good partial response (VGPR) rate with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab, when used as initial therapy in patients with previously untreated symptomatic MM. II. To determine the progression free survival and overall survival among patients with previously untreated symptomatic MM following treatment with the four drug combination of Ixazomib, lenalidomide, dexamethasone and daratumumab followed by ixazomib and daratumumab maintenance till progression. II. To determine the toxicities associated with the four drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab in patients with previously untreated symptomatic MM. TERTIARY OBJECTIVES: I. To examine the proportion of minimal residual disease (MRD) negativity following induction therapy with the four-drug combination of ixazomib, lenalidomide, dexamethasone and daratumumab. II. To assess the quality of life using patient completed Functional Assessment of Cancer Treatment (FACT)/Gynecologic Oncology Group (GOG) questionnaires. OUTLINE: INDUCTION PHASE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and lenalidomide PO on days 1-21. Patients receive daratumumab intravenously (IV) over 3-7 hours on days 1, 8, 15, and 22 of courses 1 and 2, on days 1 and 15 of courses 3, 4, and 5, and on day 1 of courses 7 and beyond. Patients also receive dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive ixazomib citrate PO on days 1, 8, and 15 and daratumumab IV over 3-7 hours on day 1. Courses repeat every 28 days for up to 36 months from registration in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 or 6 months.

Source references