NCT05561387|RecruitingPhase 3DMCFDA Drug

Comparing Combinations of Drugs to Treat Newly Diagnosed Multiple Myeloma (NDMM) When a Stem Cell Transplant is Not a Medically Suitable Treatment

A Phase III Randomized Trial for Newly Diagnosed Multiple Myeloma (NDMM) Patients Considered Frail or in a Subset of "Intermediate Fit" Comparing Upfront Three-Drug Induction Regimens Followed by Double or Single-Agent Maintenance

SWOG Cancer Research Network ClinicalTrials.gov

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3 other identifiers

S2209NCI-2022-05722U10CA180888

Study Type

interventional

Target

510

Locations

1 country

Sites

397

Timeline

RegisteredSep 2022

StartedOct 2023

CompletionMay 2031

Brief Summary

This phase III trial compares three-drug induction regimens followed by double-or single-drug maintenance therapy for the treatment of newly diagnosed multiple myeloma in patients who are not receiving a stem cell transplant and are considered frail or intermediate-fit based on age, comorbidities, and functional status. Treatment for multiple myeloma includes initial treatment (induction) which is the first treatment a patient receives for cancer followed by ongoing treatment (maintenance) which is given after initial treatment to help keep the cancer from coming back. There are three combinations of four different drugs being studied. Bortezomib is one of the drugs that may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide works by helping bone marrow to produce normal blood cells and killing cancer cells. Anti-inflammatory drugs, such as dexamethasone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Daratumumab and hyaluronidase-fihj is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Patients receive 1 of 3 combinations of these drugs for treatment to determine which combination of study drugs works better to shrink and control multiple myeloma.

Trial Health

On Track

Trial Health Score

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

Enrollment

510

participants targeted

Target at P50-P75 for phase_3

Timeline

60mo left

Started Oct 2023

Longer than P75 for phase_3

Geographic Reach

1 country

397 active sites

Status

recruiting

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

7.6 years study duration

Study Progress35%

Oct 2023May 2031

First Submitted

Initial submission to the registry

September 27, 2022

Completed

3 days until next milestone

First Posted

Study publicly available on registry

September 30, 2022

Completed

1 year until next milestone

Study Start

First participant enrolled

October 12, 2023

Completed

7.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 30, 2031

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2031

Last Updated

June 10, 2026

Status Verified

June 1, 2026

Enrollment Period

7.6 years

First QC Date

September 27, 2022

Last Update Submit

June 8, 2026

Conditions

Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

Progression free survival (PFS) of Arm 1 versus (vs.) Arm 2
Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by fluorescence in situ hybridization (iFISH) (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, or assessed up to 10 years
Overall survival (OS) of Arm 1 vs. Arm 3
Analysis of each of the dual primary endpoints will be performed using a stratified log-rank test for comparison between arms. The analyses will be stratified according to frailty score (frail vs. intermediate fit), presence of one or more high-risk abnormalities by iFISH (yes vs. no), and prior therapy (yes vs. no). All eligible participants will be considered in analyses of the dual primary endpoints, according to their assigned arm at randomization.
From date of randomization to date of death due to any cause, or assessed up to 10 years

Secondary Outcomes (9)

PFS
From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, or assessed up to 10 years
OS
From date of randomization to date of death due to any cause, or assessed up to 10 years
Overall response rate (ORR)
Up to 10 years
Time to complete response (CR)
The time from the date of registration to the date of the first documented incidence of a response of CR or better, assessed up to 10 years
Time to very good partial response (VGFR)
The time from the date of registration to the date of the first documented incidence of a response of VGPR or better, assessed up to 10 years
+4 more secondary outcomes

Study Arms (3)

Arm I (VRd-Lite)

ACTIVE COMPARATOR

INDUCTION CYCLES 1-9: Patients receive bortezomib SC on days 1, 8, 15, and 22 of each cycle, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: BortezomibDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Arm II (DRd-R)

EXPERIMENTAL

INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Daratumumab and Hyaluronidase-fihjDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Arm III (DRd-DR):

EXPERIMENTAL

INDUCTION CYCLES 1-9: Patients receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7-9, lenalidomide PO on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE CYCLES 10+: Patients receive daratumumab and hyaluronidase-fihj SC on day 1 of each cycle and lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Daratumumab and Hyaluronidase-fihjDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life AssessmentOther: Questionnaire Administration

Interventions

BortezomibDRUG

Given SC

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 (VRd-Lite)

Daratumumab and Hyaluronidase-fihjDRUG

Given SC

Also known as: DARA Co-formulated with rHuPH20, DARA/rHuPH20, Daratumumab + rHuPH20, Daratumumab with rHuPH20, Daratumumab-rHuPH20, Daratumumab/Hyaluronidase-fihj, Daratumumab/rHuPH20 Co-formulation, Darzalex Faspro, Darzalex/rHuPH20, HuMax-CD38-rHuPH20, Recombinant Human Hyaluronidase Mixed with Daratumumab

Arm II (DRd-R)Arm III (DRd-DR):

DexamethasoneDRUG

Given PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, 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, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm I (VRd-Lite)Arm II (DRd-R)Arm III (DRd-DR):

LenalidomideDRUG

Given PO

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

Arm I (VRd-Lite)Arm II (DRd-R)Arm III (DRd-DR):

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (VRd-Lite)Arm II (DRd-R)Arm III (DRd-DR):

Questionnaire AdministrationOTHER

Ancillary studies

Arm I (VRd-Lite)Arm II (DRd-R)Arm III (DRd-DR):

Eligibility Criteria

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

Participants must have documented multiple myeloma satisfying standard International Myeloma Working Group (IMWG) diagnostic criteria within 28 days prior to registration
Participants must have measurable disease within 28 days prior to registration as defined by any of the following:
Immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein \[M-protein\] level \>= 0.5 gram/deciliter \[g/dL\] or urine M-protein level \>= 200 milligram\[mg\]/24 hours\[hrs\]); OR
IgA, IgM, IgD, or IgE multiple myeloma (serum M-protein level \>= 0.2 g/dL or urine M-protein level \>= 200 mg/24 hrs); OR
Light chain multiple myeloma (serum immunoglobulin free light chain \>= 10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio)
All disease must be assessed and documented on the baseline/pre-registration tumor assessment form
Participants must have a calculated myeloma frailty index (Myeloma Frailty Score Calculator; http://www.myelomafrailtyscorecalculator.net/) categorized as frail or intermediate fit (regardless of age) within 28 days prior to registration
For Participants Meeting "Frail" Status:
Participants with any degree of kidney dysfunction are allowed; however, participants on dialysis are not eligible
For Participants Meeting "Frail" Status:
Hemoglobin \>= 7 g/dL (must be performed within 28 days prior to registration)
Note: growth factor and transfusion utilization are allowed if cytopenias are considered secondary to bone marrow involvement from MM)
For Participants Meeting "Frail" Status:
Platelets \>= 50 x 10\^9/L (must be performed within 28 days prior to registration)
Note: growth factor and transfusion utilization are allowed if cytopenias are considered secondary to bone marrow involvement from MM)
+26 more criteria

You may not qualify if:

Participants must not have received any prior systemic therapy for multiple myeloma with the exception of any one or more of the following:
An emergency use of a short course of corticosteroids (equivalent of dexamethasone 160 mg) any time before registration, or
Up to one complete cycle of a non-daratumumab and hyaluronidase-fihj containing anti-myeloma regimen (1 cycle = 21 or 28 days depending on the regimen being used), or
Localized palliative radiation therapy for multiple myeloma, as long as the radiation therapy is completed at least 3 days prior to starting the systemic treatment as per the study protocol.
Participants must not have evidence of grade 4 peripheral neuropathy prior to study registration
Participants must not have uncontrolled blood pressure within 14 days prior to registration. Uncontrolled blood pressure: systolic blood pressure (SBP) \> 140 mmHg or diastolic blood pressure (DBP) \> 90 mmHg. Participants are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study). All blood pressure measurements within the 14 days prior to registration must be SBP =\< 140 and DBP =\< 90. A participant with a single blood pressure elevation who upon rechecking has a normal blood pressure will remain eligible at the discretion of the registering investigator.
Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 24 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

SWOG Cancer Research Networklead
National Cancer Institute (NCI)collaborator

Study Sites (397)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

RECRUITING

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

RECRUITING

Alaska Breast Care and Surgery LLC