NCT04566328|RecruitingPhase 3DMCFDA Drug

Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial

Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase 3 Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation

ECOG-ACRIN Cancer Research Group ClinicalTrials.gov

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3 other identifiers

EAA181NCI-2020-06647U10CA180820

Study Type

interventional

Target

1,450

Locations

2 countries

Sites

600

Timeline

RegisteredSep 2020

StartedFeb 2021

CompletionDec 2027

Brief Summary

This phase III trial compares the combination of four drugs (daratumumab, bortezomib, lenalidomide and dexamethasone) to the use of a three drug combination (daratumumab, lenalidomide and dexamethasone). Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as lenalidomide, 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. Daratumumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. 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. Adding bortezomib to daratumumab, lenalidomide, and dexamethasone may be more effective in shrinking the cancer or preventing it from returning, compared to continuing on daratumumab, lenalidomide, and dexamethasone.

Trial Health

On Track

Trial Health Score

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

Enrollment

1,450

participants targeted

Target at P75+ for phase_3

Timeline

20mo left

Started Feb 2021

Longer than P75 for phase_3

Geographic Reach

2 countries

600 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

6.9 years study duration

Study Progress76%

Feb 2021Dec 2027

First Submitted

Initial submission to the registry

September 16, 2020

Completed

12 days until next milestone

First Posted

Study publicly available on registry

September 28, 2020

Completed

5 months until next milestone

Study Start

First participant enrolled

February 24, 2021

Completed

6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2027

Last Updated

May 5, 2026

Status Verified

April 1, 2026

Enrollment Period

6.9 years

First QC Date

September 16, 2020

Last Update Submit

April 30, 2026

Conditions

RISS Stage II Plasma Cell Myeloma Plasma Cell Myeloma RISS Stage I Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (1)

Consolidation overall survival
Will be estimated using the Kaplan-Meier (KM) method and compared using a stratified log-rank test. Stratified cox proportional hazards regression will produce treatment hazard ratio (bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide and dexamethasone \[Btz-DRd\] then daratumumab, lenalidomide and dexamethasone \[DRd\] then daratumumab and lenalidomide \[DR\]).
Time from Step 2 randomization at the start of consolidation to death or to the date last known alive, assessed up to 15 years

Secondary Outcomes (6)

Consolidation progression-free survival
Time from Step 2 randomization at the start of consolidation until the earlier of progression or death due to any cause, assessed up to 15 years
Incidence of adverse events
During induction, consolidation, and maintenance; a period of up to 42 months (9 months of induction, 9 months of consolidation, and up to 2 years of maintenance).
Incidence of grade 3 or higher non-hematologic adverse events
During induction, consolidation, and maintenance; a period of up to 42 months (9 months of induction, 9 months of consolidation, and up to 2 years of maintenance).
Incidence of grade 3 or higher adverse events
During induction, consolidation, and maintenance; a period of up to 42 months (9 months of induction, 9 months of consolidation, and up to 2 years of maintenance).
Best response
During induction, consolidation, and maintenance; a period of up to 42 months (9 months of induction, 9 months of consolidation, and up to 2 years of maintenance).
+1 more secondary outcomes

Other Outcomes (6)

Change in Functional Assessment of Cancer Therapy - Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) score (Patient reported outcome)
From end of induction to after completion of 9 cycles of consolidation, a period of approximately 36 weeks (9 months)
Levels and changes of FACT-General (G) (physical well-being [PWB] + functional well-being [FWB]) score (PRO)
From the end of induction through 1 year of maintenance, 21 weeks
Presence, frequency, interference, amount and/or severity of select PRO- Common Terminology Criteria for Adverse Events (CTCAEs) (PRO)
Up to 15 years
+3 more other outcomes

Study Arms (3)

Arm A (daratumumab, lenalidomide, dexamethasone)

ACTIVE COMPARATOR

INDUCTION: All patients receive standard induction therapy comprising the following: daratumumab subcutaneously (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 orally (PO) daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Daratumumab and Hyaluronidase-fihjDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life Assessment

Arm B (bortezomib, daratumumab, lenalidomide, dexamethasone)

EXPERIMENTAL

CONSOLIDATION: Patients receive bortezomib SC on days 1, 8, and 15, daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21 and daratumumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: BortezomibBiological: Daratumumab and Hyaluronidase-fihjDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life Assessment

Arm C (daratumumab, lenalidomide, dexamethasone)

ACTIVE COMPARATOR

CONSOLIDATION: Patients receive daratumumab SC on day 1, lenalidomide PO daily on days 1-21, and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for 9 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lenalidomide PO daily on days 1-21, and daratumumab SC on day 1. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Daratumumab and Hyaluronidase-fihjDrug: DexamethasoneDrug: LenalidomideOther: Quality-of-Life Assessment

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 B (bortezomib, daratumumab, lenalidomide, dexamethasone)

Daratumumab and Hyaluronidase-fihjBIOLOGICAL

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 A (daratumumab, lenalidomide, dexamethasone)Arm B (bortezomib, daratumumab, lenalidomide, dexamethasone)Arm C (daratumumab, lenalidomide, dexamethasone)

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, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A (daratumumab, lenalidomide, dexamethasone)Arm B (bortezomib, daratumumab, lenalidomide, dexamethasone)Arm C (daratumumab, lenalidomide, dexamethasone)

LenalidomideDRUG

Given PO

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

Arm A (daratumumab, lenalidomide, dexamethasone)Arm B (bortezomib, daratumumab, lenalidomide, dexamethasone)Arm C (daratumumab, lenalidomide, dexamethasone)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (daratumumab, lenalidomide, dexamethasone)Arm B (bortezomib, daratumumab, lenalidomide, dexamethasone)Arm C (daratumumab, lenalidomide, dexamethasone)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

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

You may qualify if:

STEP 0 - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (PS 3 allowed if secondary to pain)
STEP 0 - Patient must have newly diagnosed multiple myeloma (MM) by International Myeloma Working Group (IMWG) criteria
STEP 0 - Patient must agree to register to the mandatory REVLIMID Risk Evaluation and Mitigation Strategy (RevREMS) program and be willing and able to comply with the requirements of RevREMS
STEP 0 - Patient must be able to undergo diagnostic bone marrow aspirate following preregistration.
NOTE: Bone marrow aspirate specimen must be submitted to Adaptive Biotechnologies for clonoSEQ Assay
NOTE: Adaptive Biotechnologies will release results to the diagnostic Portal from the Clonality (ID) test within fourteen (14) days of receipt and reconciliation of fresh bone marrow specimen to the submitting institution
STEP 1 - Patient must meet all eligibility criteria in STEP 0 with exception of allergy requirement
STEP 1 - Institution must have received the Clonality (ID) test results from Adaptive Biotechnologies and dominant sequences were identified
STEP 1 - Patient must have standard risk MM as defined by the Revised International Staging System (RISS) stage I or II
NOTE: R-ISS stage is based on serum beta2 microglobulin, albumin and lactate dehydrogenase (LDH) levels along with presence of chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization (iFISH). Presence of del(17p), t(4;14), and/or t(14;16) is considered high risk and absence of these, including any other findings, are standard risk
R-ISS stage
Stage I: ISS stage I \[beta2 macroglobulin \< 3.5 mg/L, albumin \> 3.5 g/dL\] AND standard-risk CA AND normal LDH
Stage II: Not R-ISS stage I or III
Stage III: ISS stage III \[beta2 macroglobulin \> 5.5 mg/L\] AND high-risk CA OR high LDH (\> upper limit of normal) \[patients with stage III are ineligible\]
STEP 1 - Patient must have measurable or evaluable disease as defined by having one or more of the following, obtained within 28 days prior to registration:
+32 more criteria

You may not qualify if:

STEP 0 - Patient must not have any 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
STEP 1 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females 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 Step 1 registration to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
Has achieved menarche at some point,
Has not undergone a hysterectomy or bilateral oophorectomy; or
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)
STEP 1 - Women of childbearing potential must not expect to conceive children by using accepted and effective method(s) of contraception (for this protocol defined as the use of 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 protocol treatment; 2) while participating in the study; 3) during dose interruptions; and 4) for at least 3 months days after the last dose of protocol treatment) OR by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception). Men must not expect to father children by practicing true abstinence from sexual intercourse for the duration of their participation in the study (periodic abstinence \[e.g., calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception) OR use a latex condom during sexual contact with a female of child bearing potential while participating in the study and for at least 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Men must also agree to abstain from donating sperm while on study treatment and for 3 months after the last dose of protocol treatment even if they have had a successful vasectomy. Both women and men must both agree to abstain from donating blood during study participation and for at least 28 days after the last dose of protocol treatment
STEP 1 - Patient must not have peripheral neuropathy \>= grade 2 on clinical examination or grade 1 with pain at time of Step 1 registration
STEP 1 - Patient must not have any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
STEP 1 - Patient must not have moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification
NOTE: Patients who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to register
STEP 1 - Patient must not receive any other concurrent chemotherapy, or any ancillary therapy considered investigational while on this protocol
NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
STEP 2 - Patient must not have received any non-protocol therapy outside of the assigned Step 1 Induction treatment including stem cell transplant
STEP 2 - Women must not be pregnant or breast-feeding due to the potential harm and teratogenic effects to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All females 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 Step 2 randomization to rule out pregnancy and again within 24 hours prior to the first dose of lenalidomide. Females of childbearing potential must also agree to ongoing pregnancy testing while on protocol treatment. A female of childbearing potential is defined as any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
Has achieved menarche at some point,
+4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

ECOG-ACRIN Cancer Research Grouplead
National Cancer Institute (NCI)collaborator

Study Sites (600)

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