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Testing the Addition of Ixazo...

Testing the Addition of Ixazomib/Placebo to Lenalidomide in Patients With Evidence of Residual Multiple Myeloma, OPTIMUM Trial

Last Updated: 2025-05-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-16

Study Completion Date

2025-01-31

Brief Summary

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This phase III trial studies how well lenalidomide in combination with ixazomib works compared to lenalidomide alone in treating patients with evidence of residual multiple myeloma after stem cell transplantation. Lenalidomide may help shrink or slow the growth of multiple myeloma. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving lenalidomide and ixazomib together may work better than giving lenalidomide alone in treating patients with evidence of residual multiple myeloma after a stem cell transplantation.

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Detailed Description

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PRIMARY OBJECTIVE:

I. To evaluate whether escalating maintenance therapy with the addition of ixazomib citrate (ixazomib) to lenalidomide improves overall survival (OS) among patients who are minimal residual disease (MRD) positive after approximately 1 year of lenalidomide maintenance following an early stem cell transplant (=\< 12 months from diagnosis).

SECONDARY OBJECTIVES:

I. To establish whether progression-free survival (PFS) is superior with the addition of ixazomib to lenalidomide maintenance.

II. To evaluate best response on treatment and compare response rates between arms.

III. To evaluate the safety profile of ixazomib added to lenalidomide and compare toxicity rates between arms.

EXPLORATORY OBJECTIVES:

I. To measure treatment exposure and adherence. II. To estimate treatment duration, duration of response and time to progression.

PATIENT-REPORTED OUTCOMES (PRO) OBJECTIVES:

I. To quantify the extent to which the addition of ixazomib to lenalidomide maintenance contributes to neuropathy and associated physical and functional impairments. (Primary) II. To assess the impact of the addition of ixazomib to lenalidomide maintenance on disease control and associated physical and functional well-being. (Primary) III. To evaluate time to worsening and recovery rate related to neuropathy. (Secondary) IV. To evaluate time to improvement and response rate related to disease control. (Secondary) V. To evaluate attributes of select patient reported treatment-emergent symptomatic adverse events (Patient-Reported Outcomes - Common Terminology Criteria for Adverse Events \[PRO-CTCAE\]) longitudinally and compare responses with provider-reported adverse events. (Exploratory) VI. To measure the likelihood of medication adherence and examine the relationship with treatment exposure. (Exploratory) VII. To assess correlation among patient reported outcome measures and association with clinical outcomes. (Exploratory) VIII. To tabulate PRO compliance and completion rates. (Exploratory)

IMAGING OBJECTIVES:

I. To evaluate the association between baseline fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) and patient outcomes.

II. To compare overall survival (OS) with the addition of ixazomib to lenalidomide among baseline 18F-FDG PET/CT-positive and 18F-FDG PET/CT -negative subgroups.

III. To compare the change in quantitative 18F-FDG PET/CT parameters over time with the addition of ixazomib to lenalidomide.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-28 and ixazomib citrate PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and positron emission tomography (PET) and computed tomography (CT) scan at screening and on study as well as undergo collection of blood samples throughout the trial.

ARM B: Patients receive lenalidomide PO QD on days 1-28 and a placebo PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and PET and CT scan at screening and on study as well as undergo collection of blood samples throughout the trial.

After completion of study treatment, patients are followed up every 3 months if \< 2 years from study entry, every 6 months if 2-5 years from study entry, then every 12 months for up to 10 years from study entry.

Conditions

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Multiple Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm A (lenalidomide, ixazomib citrate)

Patients receive lenalidomide PO QD on days 1-28 and ixazomib citrate PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and PET and CT scan at screening and on study as well as undergo collection of blood samples throughout the trial.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Bone Marrow Aspirate

Intervention Type PROCEDURE

Undergo bone marrow aspirate

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Ixazomib Citrate

Intervention Type DRUG

Given PO

Lenalidomide

Intervention Type DRUG

Given PO

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Arm B (lenalidomide, placebo)

Patients receive lenalidomide PO QD on days 1-28 and a placebo PO on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and/or biopsy and PET and CT scan at screening and on study as well as undergo collection of blood samples throughout the trial.

Group Type PLACEBO_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood samples

Bone Marrow Aspirate

Intervention Type PROCEDURE

Undergo bone marrow aspirate

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Lenalidomide

Intervention Type DRUG

Given PO

Placebo Administration

Intervention Type OTHER

Given PO

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Quality-of-Life Assessment

Intervention Type OTHER

Ancillary studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

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Biospecimen Collection

Undergo collection of blood samples

Intervention Type PROCEDURE

Bone Marrow Aspirate

Undergo bone marrow aspirate

Intervention Type PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

Intervention Type PROCEDURE

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Ixazomib Citrate

Given PO

Intervention Type DRUG

Lenalidomide

Given PO

Intervention Type DRUG

Placebo Administration

Given PO

Intervention Type OTHER

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Quality-of-Life Assessment

Ancillary studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection BONE MARROW, LIQUID Human Bone Marrow Aspirate Biopsy of Bone Marrow Biopsy, Bone Marrow CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan tomography MLN 9708 MLN-9708 MLN9708 Ninlaro CC 5013 CC-5013 CC5013 CDC 501 Revlimid Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT Quality of Life Assessment

Eligibility Criteria

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Inclusion Criteria

* STEP 0: PRE-REGISTRATION
* Patient must be \>= 18 years of age
* Patient must be previously diagnosed with multiple myeloma (MM) and be on lenalidomide maintenance with \>= 5mg daily for at least 6 months and no more than 18 months after an early autologous stem cell transplantation (SCT =\< 12 months of diagnosis). Patient must not be off lenalidomide maintenance therapy for more than 30 days prior to start of treatment on Step 1 of this protocol
* Patient must be able to undergo a diagnostic bone marrow aspirate following pre-registration to Step 0

* NOTE: A bone marrow aspirate specimen must be submitted to Mayo Clinic Hematology Laboratory for central assessment of minimal residual disease (MRD) status to confirm patient's eligibility for Step 1 randomization. Mayo Clinic will forward results to the submitting institution within three (3) business days of receipt of the bone marrow specimen
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
* Patient must have been able to maintain at least 5mg daily dose of lenalidomide without growth factor support
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* STEP 1 RANDOMIZATION
* Patient must meet Step 0 eligibility criteria at the time of Step 1 randomization
* Patients must have evidence of residual disease by central MRD testing or by presence of monoclonal protein in serum or urine
* Patient must have serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and serum free light chain (FLC) performed =\< 28 days prior to randomization

* NOTE: UPEP (on a 24-hour collection) is required, no substitute method is acceptable. Urine must be followed monthly if the baseline urine M-spike is \>= 200 mg/24 hour (hr). Please note that if both serum and urine M-components are present, both must be followed in order to evaluate response
* Hemoglobin \>= 8 g/dL (obtained =\< 14 days prior to randomization)
* Untransfused platelet count \>= 75,000 cells/mm\^3 (obtained =\< 14 days prior to randomization)
* Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 (obtained =\< 14 days prior to randomization)
* Calculated creatinine clearance \>= 30 mL/min (obtained =\< 14 days prior to randomization)
* Total bilirubin =\< 1.5 times the upper limit of normal (ULN) (obtained =\< 14 days prior to randomization)
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 times the upper limit of normal (ULN) (obtained =\< 14 days prior to randomization)
* Patient must agree to register into the mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) registered trademark program and be willing and able to comply with the requirements of Revlimid REMS registered trademark
* Patients of childbearing potential must either abstain from sexual intercourse for the duration of their participation in the study or agree to use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME for 1) at least 28 days before starting study treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 90 days after the last dose of protocol treatment. Patients must also agree to not breastfeed during this same time period. Men must agree to either abstain from sexual intercourse for the duration of their participation in the study or use a latex condom during sexual contact with a partner of childbearing potential while participating in the study and for 90 days after the last dose of protocol treatment even if they have had a successful vasectomy. Patients must also agree to abstain from donating sperm while on study treatment and for 28 days after the last dose of protocol treatment even if they have had a successful vasectomy. All patients must agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment

Exclusion Criteria

* Patient must not have primary refractory or progressive disease on a proteasome inhibitor-based regimen during induction therapy prior to stem cell transplant
* Patient must not be on other concurrent chemotherapy, or any ancillary therapy considered investigational

* NOTE: Bisphosphonates are considered to be supportive care rather than therapy and are allowed while on protocol treatment
* Patient must not have uncontrolled psychiatric illness or social situations that would limit compliance with study requirements
* Patient must not have another malignancy requiring treatment or have received treatment within two years before pre-registration or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
* Patients must not have known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or lenalidomide including difficulty swallowing
* Patient must not have known hepatitis B surface antigen-positive status or known or suspected active hepatitis C infection, but testing specifically for the trial is not required
* Patient must not be off lenalidomide maintenance therapy for more than 30 days prior to start of treatment on Step 1 of this protocol
* Patients must not have grade 2 or higher peripheral neuropathy or grade 1 peripheral neuropathy with pain per Common Terminology Criteria for Adverse Events (CTCAE)
* Patients must not have uncontrolled intercurrent illness
* Patients must not have grade 2 or higher diarrhea per CTCAE in the absence of antidiarrheals
* Patients must not have been on systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (such as rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
* Patient must not be pregnant due to potential harm to the fetus from ixazomib and lenalidomide. All patients of childbearing potential must have a blood test or urine study with a sensitivity of at least 25 mIU/mL within 10-14 days prior to the first dose of lenalidomide and again within 24 hours prior to the first dose of lenalidomide. Patients of childbearing potential must also agree to ongoing pregnancy testing while on treatment. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shaji K Kumar

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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Cancer Center at Saint Joseph's

Phoenix, Arizona, United States

Site Status

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

Site Status

Mission Hope Medical Oncology - Arroyo Grande

Arroyo Grande, California, United States

Site Status

Pacific Central Coast Health Center-San Luis Obispo

San Luis Obispo, California, United States

Site Status

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California, United States

Site Status

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

Site Status

AdventHealth Porter

Denver, Colorado, United States

Site Status

Mercy Medical Center

Durango, Colorado, United States

Site Status

Southwest Oncology PC

Durango, Colorado, United States

Site Status

Saint Anthony Hospital

Lakewood, Colorado, United States

Site Status

Littleton Adventist Hospital

Littleton, Colorado, United States

Site Status

Longmont United Hospital

Longmont, Colorado, United States

Site Status

Rocky Mountain Cancer Centers-Longmont

Longmont, Colorado, United States

Site Status

Parker Adventist Hospital

Parker, Colorado, United States

Site Status

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

Site Status

Rush - Copley Medical Center

Aurora, Illinois, United States

Site Status

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Site Status

Illinois CancerCare-Canton

Canton, Illinois, United States

Site Status

Memorial Hospital of Carbondale

Carbondale, Illinois, United States

Site Status

SIH Cancer Institute

Carterville, Illinois, United States

Site Status

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Site Status

Centralia Oncology Clinic

Centralia, Illinois, United States

Site Status

Carle at The Riverfront

Danville, Illinois, United States

Site Status

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Illinois CancerCare-Dixon

Dixon, Illinois, United States

Site Status

Carle Physician Group-Effingham

Effingham, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Site Status

Illinois CancerCare-Galesburg

Galesburg, Illinois, United States

Site Status

Western Illinois Cancer Treatment Center

Galesburg, Illinois, United States

Site Status

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Site Status

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Site Status

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

Site Status

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Site Status

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Site Status

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Illinois CancerCare-Peru

Peru, Illinois, United States

Site Status

Valley Radiation Oncology

Peru, Illinois, United States

Site Status

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Springfield Clinic

Springfield, Illinois, United States

Site Status

Springfield Memorial Hospital

Springfield, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

The Carle Foundation Hospital

Urbana, Illinois, United States

Site Status

Illinois CancerCare - Washington

Washington, Illinois, United States

Site Status

Rush-Copley Healthcare Center

Yorkville, Illinois, United States

Site Status

Mary Greeley Medical Center

Ames, Iowa, United States

Site Status

McFarland Clinic - Ames

Ames, Iowa, United States

Site Status

McFarland Clinic - Boone

Boone, Iowa, United States

Site Status

Saint Anthony Regional Hospital

Carroll, Iowa, United States

Site Status

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Site Status

Mission Cancer and Blood - West Des Moines

Clive, Iowa, United States

Site Status

Alegent Health Mercy Hospital

Council Bluffs, Iowa, United States

Site Status