NCT01668719|CompletedPhase 1ResultsDMC

S1211 Bortezomib, Dexamethasone, and Lenalidomide With or Without Elotuzumab in Treating Patients With Newly Diagnosed High-Risk Multiple Myeloma

A Randomized Phase I/II Study of Optimal Induction Therapy of Bortezomib, Dexamethasone and Lenalidomide With or Without Elotuzumab (NSC-764479) for Newly Diagnosed High Risk Multiple Myeloma (HRMM)

SWOG Cancer Research Network ClinicalTrials.gov

Compare

6 other identifiers

S1211NCI-2012-01998PS1211_A12PAMDREVW01CDR0000738512U10CA180888U10CA032102

Study Type

interventional

Target

142

Locations

1 country

Sites

417

Timeline

RegisteredAug 2012

StartedNov 2012

CompletionSep 2025

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of elotuzumab and to see how well it works when given together with lenalidomide, bortezomib, and dexamethasone in treating patients with newly diagnosed multiple myeloma that is likely to recur (come back), or spread (high-risk). Lenalidomide and bortezomib may stop the growth of multiple myeloma by blocking blood flow to the tumor. Also, bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide and dexamethasone, also work in different ways to kill cancer cells, by stopping them from dividing, or by stopping them from spreading. Giving elotuzumab together with lenalidomide, bortezomib, and dexamethasone may be a better way to block cancer growth.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

142

participants targeted

Target at P75+ for phase_1

Timeline

Completed

Started Nov 2012

Longer than P75 for phase_1

Geographic Reach

1 country

417 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

12.9 years study duration

First Submitted

Initial submission to the registry

August 16, 2012

Completed

4 days until next milestone

First Posted

Study publicly available on registry

August 20, 2012

Completed

2 months until next milestone

Study Start

First participant enrolled

November 1, 2012

Completed

7.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 5, 2020

Completed

1.7 years until next milestone

Results Posted

Study results publicly available

October 27, 2021

Completed

3.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 22, 2025

Completed

Last Updated

April 28, 2026

Status Verified

April 1, 2026

Enrollment Period

7.3 years

First QC Date

August 16, 2012

Results QC Date

June 8, 2021

Last Update Submit

April 15, 2026

Conditions

DS Stage I Plasma Cell Myeloma DS Stage II Plasma Cell Myeloma DS Stage III Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

Phase I: Maximum Tolerated Dose (MTD) of Elotuzumab in Combination With Bortezomib, Lenalidomide and Dexamethasone
Assess safety of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone and select the optimal dose of elotuzumab for the Phase II portion from 10mg/kg on each cycle, to 5mg/kg on each cycle MTD reflects the highest dose that had a dose-limiting toxicity (DLT) rate of ≤ 1/6 participants. DLTs were defined as treatment regimen related: grade ≥ 3 non-hematologic toxicity; grade 3 nausea or diarrhea despite anti-emetic and anti-diarrheal therapy; grade 3 hyperglycemia if symptomatic or glucose level \> 300mg/ml despite insulin and/or oral diabetic therapy; grade 4 neutropenia ≥ 7 days or grade 3/4 neutropenia with fever (≥ 38.5 oC); grade 4 thrombocytopenia ≥ 7 days or associated with hemorrhage; delay of treatment with any agent by \> 2 weeks due to drug related toxicity. DLT were graded using the NCI CTCAE version 4.0 Note: i) the second, lower dose level was not tested as the first dose level was deemed safe ii) 6 participants were evaluable at phase I analysis
time from first participants randomized until at least 6 patients were evaluable for DLTs. DLTs were assessed only during Cycle 1 (21 days)
Progression-free Survival
From date of registration to date of first documentation of progression or death due to any cause. Per the International Uniform Response Criteria for Multiple Myeloma, progression is defined as \>=1 of Serum M protein increase \>= 25% from lowest response level, with an absolute increase of \>= 0.5g/dL; Urine M protein increase \>= 25% from lowest response level, with an absolute increase of \>= 200 mg/24 hrs; If participant had serum M protein \<1 g/dL, urine M protein \<200 mg/24 hrs, and an involved serum free light chain level \>= 10mg/dL at baseline: \>= 25% increase in the difference between involved and uninvolved serum free light chain level with an absolute increase of \>= 10 mg/dL; Bone marrow plasma cell % increase =25% from baseline with the absolute plasma cell % \>=10%; New bone lesions or soft tissue plasmocytomas, or definite increase in size of existing bone lesions or soft tissue plasmocytomas; Development of hypercalcemia that can be attributed solely to multiple myeloma
Up to 6 years post registration

Secondary Outcomes (3)

Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Duration of treatment and follow up until death or 6 years post registration, whichever occurs first.
Overall Survival
Up to 6 years post registration
Response (Partial Response [PR] or Better) Rate
Up to 6 years post registration

Study Arms (2)

Arm I (bortezomib, lenalidomide, dexamethasone)

ACTIVE COMPARATOR

INDUCTION: Patients receive bortezomib SC or IV on days 1, 4, 8, and 11; lenalidomide PO QD on days 1-14; and dexamethasone PO or IV on days 1, 2, 4, 5, 8, 9, 11, and 12. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity (patients who received a course of chemotherapy prior to registration will begin protocol treatment with course 2 and receive a total of 7 courses of protocol therapy). MAINTENANCE: Patients receive bortezomib SC or IV on days 1, 8, and 15; lenalidomide PO QD on days 1-21; and dexamethasone PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: BortezomibDrug: DexamethasoneOther: Laboratory Biomarker AnalysisDrug: Lenalidomide

Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

EXPERIMENTAL

INDUCTION: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1, 8, and 15 of courses 1 and 2 and on days 1 and 11 of courses 3-8. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive bortezomib, lenalidomide, and dexamethasone as in Arm I. Patients also receive elotuzumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: BortezomibDrug: DexamethasoneBiological: ElotuzumabOther: Laboratory Biomarker AnalysisDrug: Lenalidomide

Interventions

BortezomibDRUG

Given SC or IV

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade

Arm I (bortezomib, lenalidomide, dexamethasone)Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

DexamethasoneDRUG

Given PO or IV

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

Arm I (bortezomib, lenalidomide, dexamethasone)Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

ElotuzumabBIOLOGICAL

Given IV

Also known as: BMS-901608, HuLuc63, PDL-063, PDL063

Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (bortezomib, lenalidomide, dexamethasone)Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

LenalidomideDRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Arm I (bortezomib, lenalidomide, dexamethasone)Arm II (bortezomib, lenalidomide, dexamethasone, elotuzumab)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patients must have newly diagnosed active multiple myeloma (MM)
For the Phase II portion only, patients must have high-risk MM based on one or more of the following criteria at the time of initial diagnosis (prior to any chemotherapy):
Poor-risk genomic signature according to the University of Arkansas 70-gene model (available clinically as myeloma prognostic risk score \[MyPRS\] score, Signal Genetics, Inc) AND/OR
Translocation (14;16), and/or translocation (14;20), and/or deletion (17p) by fluorescence in-situ hybridization (FISH) or cytogenetics AND/OR
Primary plasma cell leukemia (defined by either \>= 2,000 plasma cells/mL of peripheral blood, or 20% on a manual differential count) AND/OR
Serum lactate dehydrogenase (LDH) \>= 2 x institutional upper limit of normal (IULN) AND/OR
q21 amplification by FISH analysis AND/OR
High risk by the SKY92 signature
Patients with non-secretory MM or known amyloidosis are not eligible
Patients must have measurable disease within 28 days prior to registration (or prior to initiation of first induction course for patients with prior therapy)
Patients on the Phase I portion may not have received ANY prior chemotherapy; patients on the Phase II portion may have received one prior cycle of any non-investigational chemotherapy; prior chemotherapy must have been completed within 56 days prior to registration and all toxicities must have resolved to =\< grade 1; patients on either portion may have received prior treatment with dexamethasone, providing total number of days of treatment was =\< 14 days and total treatment dose was =\< 360 mg
Patients may have received prior radiotherapy for symptomatic localized bone lesions or impending spinal cord compression only; radiotherapy must be completed at least 14 days prior to registration and all toxicities must have resolved to =\< grade 1
Absolute neutrophil count (ANC) \>= 1,000 cells/mm\^3 without growth factor support
Platelet count \>= 70,000 cells/mm\^3 for patients who have bone marrow plasmacytosis \< 50%; or \>= 50,000 cells/mm\^3 for patients who have bone marrow plasmacytosis of \>= 50%
Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN)
+23 more criteria

Contact the study team to confirm eligibility.