Description:
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.
Title
- Brief Title: Testing the Use of Combination Therapy in Adult Patients With Newly Diagnosed Multiple Myeloma, the EQUATE Trial
- Official Title: Effective Quadruplet Utilization After Treatment Evaluation (EQUATE): A Randomized Phase 3 Trial for Newly Diagnosed Multiple Myeloma Not Intended for Early Autologous Transplantation
Clinical Trial IDs
- ORG STUDY ID:
EAA181
- SECONDARY ID:
NCI-2020-06647
- SECONDARY ID:
EAA181
- SECONDARY ID:
EAA181
- SECONDARY ID:
U10CA180820
- NCT ID:
NCT04566328
Conditions
- Plasma Cell Myeloma
- RISS Stage I Plasma Cell Myeloma
- RISS Stage II Plasma Cell Myeloma
Interventions
| Drug | Synonyms | Arms |
|---|
| Bortezomib | [(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-fihj | 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) |
| Dexamethasone | 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) |
| Lenalidomide | CC-5013, CC5013, CDC 501, Revlimid | Arm A (daratumumab, lenalidomide, dexamethasone) |
Purpose
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.
Detailed Description
PRIMARY OBJECTIVE:
I. To determine if bortezomib, daratumumab and hyaluronidase-fihj (daratumumab), lenalidomide
and dexamethasone (Btz-DRd) consolidation followed by daratumumab and lenalidomide (DR)
maintenance after standard induction therapy with daratumumab, lenalidomide and dexamethasone
(DRd) results in superior overall survival compared to DRd consolidation followed by DR
maintenance, in minimal residual disease (MRD) positive patients.
SECONDARY OBJECTIVES:
I. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction
therapy with DRd results in superior overall survival compared to DRd consolidation followed
by DR maintenance in MRD negative patients.
II. To determine if Btz-DRd consolidation followed by DR maintenance after standard induction
therapy with DRd results in superior progression-free survival compared to DRd consolidation
followed by DR maintenance in both MRD positive and MRD negative patients.
III. To describe and compare the incidence of toxicities during consolidation between Btz-DRd
and DRd arms.
IV. To assess the improvement in MRD negative rate with consolidation among patients who are
MRD positive after induction.
V. To assess the sustained MRD negative rate among patients who are MRD negative after
induction.
PATIENT REPORTED OUTCOMES (PRO) OBJECTIVES:
I. To quantify the extent to which the addition of bortezomib to DRd over consolidation
treatment contributes to neuropathy and associated physical and functional impairments.
(Primary PRO Objective) II. To evaluate the rate of resolution of neurotoxicity and
associated physical and functional impairments following completion of consolidation therapy.
(Secondary PRO Objective) III. To investigate the relationship between MRD status and patient
reported health-related quality of life outcomes. (Exploratory PRO Objective) IV. To evaluate
attributes of select patient reported treatment-emergent symptomatic adverse events (PRO-
Common Terminology Criteria for Adverse Events [CTCAE]) longitudinally and compare responses
with provider-reported adverse events. (Exploratory PRO Objective) V. To tabulate PRO
compliance and completion rates. (Exploratory PRO Objective)
IMAGING OBJECTIVES:
I. To evaluate the association between post-induction fludeoxyglucose F-18 (18F-FDG) positron
emission tomography (PET)/computed tomography (CT) and patient outcomes (overall survival
[OS] and progression-free survival [PFS]). (Primary Imaging Objective) II. To evaluate the
association between baseline 18F-FDG PET/CT and patient outcomes (PFS and OS). (Secondary
Imaging Objective) III. To compare overall survival with the addition of Bortezomib to
consolidation DRd therapy among 18F-FDG PET/CT-positive and 18F-FDG PET/CT-negative
subgroups. (Secondary Imaging Objective) IV. To evaluate the ability of baseline 18F-FDG
PET/CT to predict post-induction depth of response as measured by MRD assessment. (Secondary
Imaging Objective) V. To evaluate the ability of post-induction 18F-FDG PET/CT to predict MRD
conversion post-consolidation. (Secondary Imaging Objective) VI. To utilize 18F-FDG PET/CT,
standard risk factors and clinical data to identify distinct subgroups with differing patient
outcomes (PFS and OS). (Exploratory Imaging Objective) VII. To compare the various
qualitative 18F-FDG PET/CT criteria to determine which criteria yields superior risk
stratification. (Exploratory Imaging Objective)
OUTLINE:
ARM A (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.
After completion of standard induction therapy, patients are randomized to 1 of 2 arms.
ARM B:
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.
ARM C:
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.
After completion of study treatment, patients are followed up every 3 months if less than 2
years from study entry, every 6 months if 2-5 years from study entry, then annually for up to
15 years from study entry.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - Daratumumab and Hyaluronidase-fihj
- Dexamethasone
- Lenalidomide
|
| 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. | - Bortezomib
- Daratumumab and Hyaluronidase-fihj
- Dexamethasone
- Lenalidomide
|
| 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. | - Daratumumab and Hyaluronidase-fihj
- Dexamethasone
- Lenalidomide
|
Eligibility Criteria
Inclusion Criteria:
- 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:
- >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis
- >= 200 mg/24 hours of monoclonal protein on a 24-hour urine protein
electrophoresis
- Involved free light chain >= 10 mg/dL or >= 100 mg/L AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio (< 0.26 or > 1.65)
- Monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
- STEP 1 - Patients must have a serum protein electrophoresis (SPEP), urine protein
electrophoresis (UPEP), and serum free light chain (FLC) assay performed within 28
days prior to registration. In addition, a bone marrow biopsy and/or aspirate is
required within 28 days if bone marrow is being followed for response
- 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 hr. Please note that if both serum and urine M-components are present,
both must be followed in order to evaluate response
- NOTE: The serum free light chain test is required to be done if the patient does
not have measurable disease in the serum or urine. Measurable disease in the
serum is defined as having a serum M-spike >= 1 g/dL. Measurable disease in the
urine is defined as having a urine M-spike >= 200 mg/24 hr
- STEP 1 - Calculated creatinine clearance > 30 mL/min (obtained =< 14 days prior to
Step 1 registration)
- STEP 1 - Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to
Step 1 registration)
- STEP 1 - Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to Step
1 registration)
- STEP 1 - Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to Step 1 registration)
- STEP 1 - Total bilirubin =< 1.5 x ULN (institutional upper limit of normal) (obtained
=< 14 days prior to Step 1 registration)
- STEP 1 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x
ULN (obtained =< 14 days prior to Step 1 registration)
- STEP 1 - Patient must have received no more than one cycle (28 days or less) of prior
chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
prednisone) for treatment of symptomatic myeloma. Patient must not have been exposed
to daratumumab for treatment of symptomatic myeloma. Prior radiation therapy to
symptomatic lesions is allowed provided there are no residual toxicity related to
radiation and blood counts meet the study requirements. Radiation treatment must be
completed at least 14 days prior to Step 1 registration
- STEP 1 - Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months of randomization
are eligible for this trial
- STEP 1 - For patients with evidence of chronic hepatitis B virus (HBV) infection, the
HBV viral load must be undetectable on suppressive therapy, if indicated
- STEP 1 - Patients with a history of hepatitis C virus (HCV) infection must have been
treated and cured. For patients with HCV infection who are currently on treatment,
they are eligible if they have an undetectable HCV viral load
- STEP 1 - Patients with a prior or concurrent malignancy whose natural history or
treatment does not have the potential to interfere with the safety or efficacy
assessment of the investigational regimen are eligible for this trial
- STEP 1 - Patients with known history or current symptoms of cardiac disease, or
history of treatment with cardiotoxic agents, should have a clinical risk assessment
of cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, patients should be class 2B or better. Patients must not
have evidence of current uncontrolled cardiovascular conditions, including
hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or
myocardial infarction within 6 months prior to Step 1 registration
- STEP 1 - Patient may have a history of current or previous deep vein thrombosis (DVT)
or pulmonary embolism (PE) but must be willing to take some form of anti-coagulation
as prophylaxis if they are not currently on full-dose anticoagulation
- STEP 1 - Patients with a history of chronic obstructive pulmonary disease (COPD) must
have FEV1 testing done within 28 days prior to Step 1 registration and the forced
expiratory volume in 1 second (FEV1) must be > 50% of predicted normal
- STEP 2 - Institution must have received Tracking (MRD) test results from Adaptive
Biotechnologies
- STEP 2 - Patient must have completed the Step 1 Induction phase of this protocol
without experiencing progression
- STEP 2 - Patient must be registered to Step 2 within 8 weeks of completing Step 1
Induction Treatment, counting from last day of completion of last cycle
- STEP 2 - Patient must have an ECOG performance status (PS) of 0-2 (PS 3 allowed if
secondary to pain)
- STEP 2 - Any adverse event(s) related to Step 1 Induction Treatment must have resolved
to grade 2 or less
- STEP 2 - Hemoglobin >= 8 g/dL (obtained within 14 days prior to Step 2 randomization)
- STEP 2 - Platelet count >= 50,000/mm^3 (obtained within 14 days prior to Step 2
randomization)
- STEP 2 - Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained within 14 days prior
to Step 2 randomization)
- STEP 2 - Calculated creatinine clearance >= 30 mL/min (obtained within 14 days prior
to Step 2 randomization)
- STEP 2 - Total bilirubin =< 1.5 x ULN (Institutional upper limit of normal) (obtained
within 14 days prior to Step 2 randomization)
- STEP 2 - ALT and AST < 3 x ULN (obtained within 14 days prior to Step 2 randomization)
Exclusion Criteria:
- 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,
- 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 2 - 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Consolidation overall survival |
| Time Frame: | Time from Step 2 randomization at the start of consolidation to death or to the date last known alive, assessed up to 15 years |
| Safety Issue: | |
| Description: | 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]). |
Secondary Outcome Measures
| Measure: | Consolidation progression-free survival |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | Patients alive without disease progression will be censored at date of last disease evaluation. Only deaths that occur within 3 months of the last disease evaluation are considered events. |
| Measure: | Incidence of adverse events |
| Time Frame: | 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). |
| Safety Issue: | |
| Description: | |
| Measure: | Incidence of grade 3 or higher non-hematologic adverse events |
| Time Frame: | 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). |
| Safety Issue: | |
| Description: | |
| Measure: | Incidence of grade 3 or higher adverse events |
| Time Frame: | 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). |
| Safety Issue: | |
| Description: | |
| Measure: | Best response |
| Time Frame: | 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). |
| Safety Issue: | |
| Description: | |
| Measure: | FACT-Ntx TOI recovery rate (Patient reported outcome [PRO]) |
| Time Frame: | From end of induction through consolidation up to 1 year of maintenance, up to 21 weeks |
| Safety Issue: | |
| Description: | Defined as the proportion of patients with the FACT-Ntx TOI score returning to baseline level reached at consolidation randomization after experiencing a MID decrease while on up to 1 year of maintenance. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | ECOG-ACRIN Cancer Research Group |
Last Updated
August 20, 2021
