Trial Outcomes & Findings for Testing the Addition of Ixazomib/Placebo to Lenalidomide in Patients With Evidence of Residual Multiple Myeloma, OPTIMUM Trial (NCT NCT03941860)

Results Overview

Overall survival is defined as time from randomization to death or date last known alive.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1 participants

Primary outcome timeframe

Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Results posted on

2025-05-23

Participant Flow

The study was activated on June 1, 2021 and closed to accrual on March 3, 2023 due to slow accrual.

Participant milestones

Participant milestones
Measure	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. Biospecimen Collection: Undergo collection of blood samples Bone Marrow Aspirate: Undergo bone marrow aspirate Bone Marrow Biopsy: Undergo bone marrow biopsy Computed Tomography: Undergo CT scan Ixazomib Citrate: Given PO Lenalidomide: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: 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. Biospecimen Collection: Undergo collection of blood samples Bone Marrow Aspirate: Undergo bone marrow aspirate Bone Marrow Biopsy: Undergo bone marrow biopsy Computed Tomography: Undergo CT scan Lenalidomide: Given PO Placebo Administration: Given PO Positron Emission Tomography: Undergo PET scan Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Study STARTED	0	1
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	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. Biospecimen Collection: Undergo collection of blood samples Bone Marrow Aspirate: Undergo bone marrow aspirate Bone Marrow Biopsy: Undergo bone marrow biopsy Computed Tomography: Undergo CT scan Ixazomib Citrate: Given PO Lenalidomide: Given PO Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: 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. Biospecimen Collection: Undergo collection of blood samples Bone Marrow Aspirate: Undergo bone marrow aspirate Bone Marrow Biopsy: Undergo bone marrow biopsy Computed Tomography: Undergo CT scan Lenalidomide: Given PO Placebo Administration: Given PO Positron Emission Tomography: Undergo PET scan Quality-of-Life Assessment: Ancillary studies Questionnaire Administration: Ancillary studies
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline data not reported

PRIMARY outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Population: Only one patient was enrolled on this study. Due to the concern on confidentiality, individual data is not reported.

Overall survival is defined as time from randomization to death or date last known alive.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Population: Only one patient was enrolled on this study. Due to confidentiality reasons, individual data was not reported.

Progression-free survival defined as the time from randomization until the earlier of progression or death due to any cause, or censored at date of last disease evaluation. Progression is defined as one of the following criteria is met. * Increase of ≥ 25% from lowest value reported in serum M-component (the absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (the absolute increase must be ≥ 200 mg/ 24 hours). * Only in patients without measurable serum and urine M protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL. * If the only measurable disease is bone marrow, bone marrow plasma cell percentage: the absolute % must be ≥ 10%. * Development of new bone lesions or soft tissue plasmacytomas or ≥ 50% increase from nadir in the size (SPD) of existing bone lesions or soft tissue plasmacytoma or ≥ 50% increase in the longest diameter of a previous lesion \> 1cm in short axis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Population: Only one patient was enrolled on this study. Due to confidentiality reasons, individual data was not reported.

Response is evaluated based on standard International Myeloma Working Group (IMWG) criteria and tabulated by category. Response (stringent complete response \[sCR\], complete response \[CR\], very good partial response \[VGPR\]) is defined as below. sCR: All CR criteria and the following have to be met. Normal serum FLC ratio at two consecutive times and absence of clonal cells in bone marrow by immunohistochemistry or 2- to 4- color flow cytometry. Presence/absence of clonal cells is based upon the κ/λ ratio. An abnormal κ/λ ratio by immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an abnormal clone is κ/λ ratio of 4:1 or 1:2. CR: Complete disappearance of an Mprotein and no evidence of myeloma in the bone marrow. VGPR: Serum M-protein detectable by immunofixation but not quantifiable on electrophoresis and urine M-protein \< 100 mg/24 hours

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment, up to 10 years

Cumulative dose will be calculated as the sum of all doses taken across all cycles.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment, up to 10 years

Relative dose intensity will be calculated as the dose intensity divided by planned dose intensity.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 15 years

Will be calculated as cumulative dose received divided by treatment duration. Will be calculated overall and by cycle. Data will be summarized by treatment arm with descriptive statistics and graphically over time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: End of treatment, up to 10 years

Treatment duration is defined as the time from randomization to date off treatment. Patients who are still on treatment will be censored at the date of last treatment.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Duration of response is defined as the time from observed response (VGPR, CR or sCR) to the time of progression in the respective group of responders.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Time to progression is defined as the time from randomization to progression. Patients without documented progression will be censored at date of last disease assessment. Progression is defined as one of the following criteria is met. * Increase of ≥ 25% from lowest value reported in serum M-component (the absolute increase must be ≥ 0.5 g/dL) and/or urine M-component (the absolute increase must be ≥ 200 mg/ 24 hours). * Only in patients without measurable serum and urine M protein levels: the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL. * If the only measurable disease is bone marrow, bone marrow plasma cell percentage: the absolute % must be ≥ 10%. * Development of new bone lesions or soft tissue plasmacytomas or ≥ 50% increase from nadir in the size (SPD) of existing bone lesions or soft tissue plasmacytoma or ≥ 50% increase in the longest diameter of a previous lesion \> 1cm in short axis.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, end of every 3 cycles for the first 24 cycles, every 6 cycles thereafter up to completion of 48 cycles, and at treatment discontinuation prior to completing 48 cycles. During long-term follow-up, 4 quarterly assessments for 1 year.

Health-related QOL will be assessed with three instruments: 1) the FACT-General (G) functional well-being (FWB) and physical wellbeing (PWB) subscales. Each FACT-G subscale has 7 items. The 14 items are based on a 5-point Likert scale (0-4) resulting in a score ranging from 0 to 56 points with a higher score indicating better health-related QOL; 2) The FACT/GOG-Neurotoxicity Trial Outcomes Index (FACT/GOG-Ntx TOI) comprised of the FWB and PWB subscales plus the neurotoxicity subscale which has 11 items, summing to a score of 0-100; and 3) the FACT-Multiple Myeloma Trial Outcomes Index (FACT-MM TOI) comprised of the FWB and PWB subscales plus the multiple myeloma subscale which has 14 items, summing to a score of 0-112 for the instrument.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline, end of every 3 cycles for the first 24 cycles, every 6 cycles thereafter up to completion of 48 cycles, and at treatment discontinuation prior to completing 48 cycles. During long-term follow-up, 4 quarterly assessments for 1 year.

Health-related QOL will be assessed with three instruments: 1) the FACT-General (G) functional well-being (FWB) and physical wellbeing (PWB) subscales. Each FACT-G subscale has 7 items. The 14 items are based on a 5-point Likert scale (0-4) resulting in a score ranging from 0 to 56 points with a higher score indicating better health-related QOL; 2) The FACT/GOG-Neurotoxicity Trial Outcomes Index (FACT/GOG-Ntx TOI) comprised of the FWB and PWB subscales plus the neurotoxicity subscale which has 11 items, summing to a score of 0-100; and 3) the FACT-Multiple Myeloma Trial Outcomes Index (FACT-MM TOI) comprised of the FWB and PWB subscales plus the multiple myeloma subscale which has 14 items, summing to a score of 0-112 for the instrument.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every cycle up to cycle 25

NCI PRO-CTCAE items will be administered. There are 80 symptomatic AE terms included in the PRO-CTCAE library. Items correspond to 5 attributes measured \[frequency (F), severity (S), interference (I), presence/absence (P) and amount (A)\] based on multiple choice questions. Response for each attribute except P which is binary is on a 5-point Likert scale with 5 indicating 'almost constantly' frequency, 'very severe' severity, 'very much' amount or 'very much' interference. For each attribute, recall is the past 7 days. Attributes measured for each symptomatic AE varies and comprise the PRO-CTCAE item library. For this study, 23 symptomatic AEs summing to 38 items have been selected as presented below. There are 10 symptomatic AEs assessed using one item, 11 symptomatic AEs assessed using two items, and 6 symptomatic AEs assessed using three items. The types of items in order of prevalence include severity, interference, frequency, present/not present, and amount. T

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at cycles 7, 13, 19, 25, 31, 37, 43 and 49

The Adherence Starts with Knowledge Scale (ASK-12) will be used to assess the likelihood that a patient is taking oral medications per protocol. The 12-item questionnaire was derived from the predecessor ASK-20 using a study population of 112 patients with asthma, congestive heart failure or diabetes. In this study, the ASK12 had good internal consistency, and test-retest reliability. The ASK-12 which elicits the same type of information as the Morisky Medication Adherence Scale (MMAS) also demonstrated convergent validity through strong correlation with MMAS-4 (Spearman correlation r = 0.74; p \< 0.001). The ASK-12 titled 'Taking Medicine What Gets in the Way?' is segmented into 3 sections: inconvenience/forgetfulness (3 items), treatment beliefs (4 items) and behavior (5 items). Response for each item is on a 5-point Likert scale (1-5) with the total score ranging from 12-60 and a higher score representing less likelihood of medication adherence.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

The association between patient reported outcome measures and clinical outcomes will be evaluated.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At 10 years

PRO compliance rate is defined as the proportion of patients who submit the given PRO instrument among those eligible at each time point which excludes those missing by design (due to death or disease progression, early treatment discontinuation).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at each cycle, up to 10 years

PRO completion rate is defined as the proportion of patients who complete given PRO instrument based on the instrument's scoring system among those eligible at each time point.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Quantitatively, the association between baseline standardized uptake values (SUV) based quantitative 18F-FDG PET/CT parameters (SUVmax, SUVpeak, metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\]) and PFS will be analyzed through Cox regression. PFS will be defined as the time from randomization until the earlier of progression or death due to any cause. SUV-based quantitative 18F-FDG PET/CT (qPET) parameters will be analyzed as continuous covariates.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline and 1 year

The difference in qPET parameters from the baseline 18FFDG PET/CT to the year 1 18F-FDG PET/CT will be reported by study arm. An analysis of covariance (ANCOVA) model will be used to test for a treatment effect on each qPET parameter, where the baseline qPET parameter value and an indicator for study arm are included as covariates, with the qPET parameter at year 1 as the model outcome.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed every 3 months if patient is <2 years from randomization, every 6 months if patient is 2-5 years from randomization, annually if patient is 5 years or more from randomization.

Heterogeneity of treatment effect will be assessed at full information, using a two-sided statistical test for interaction between study arm (ixazomib/lenalidomide vs. placebo/lenalidomide) and baseline 18F-FDG PET/CT status (positive/abnormal vs. negative) in a Cox regression model. If the statistical test for interaction is not significant at the 0.05 level, we will conclude that there is not sufficient evidence for heterogeneity of treatment effect; if the statistical test for interaction is significant, estimated treatment hazard ratios for OS (ixazomib arm vs. placebo arm) will be reported separately for baseline 18FFDG PET/CT-positive and 18F-FDG PET/CT-negative subgroups, along with the corresponding 95% confidence intervals. OS will be defined as the time from randomization until death or the date last known alive.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at each cycle, up to 10 years

Incidence of adverse events

Outcome measures

Outcome data not reported

Adverse Events

Arm A (Lenalidomide, Ixazomib Citrate)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Arm B (Lenalidomide, Placebo)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60