Clinical Trials /

Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma

NCT01863550

Description:

This randomized phase III trial studies bortezomib, lenalidomide, and dexamethasone to see how well they work compared to carfilzomib, lenalidomide, and dexamethasone in treating patients with newly diagnosed multiple myeloma. Bortezomib and carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells. Drugs used in chemotherapy, such as dexamethasone, 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. It is not yet known whether bortezomib, lenalidomide, and dexamethasone are more or less effective than carfilzomib, lenalidomide, and dexamethasone in treating patients with multiple myeloma

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Bortezomib or Carfilzomib With Lenalidomide and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma
  • Official Title: Randomized Phase III Trial of Bortezomib, Lenalidomide, and Dexamethasone (VRd) Versus Carfilzomib, Lenalidomide, and Dexamethasone (CRd) Followed by Limited or Indefinite Duration Lenalidomide Maintenance in Patients With Newly Diagnosed Symptomatic Multiple Myeloma (ENDURANCE)

Clinical Trial IDs

  • ORG STUDY ID: E1A11
  • SECONDARY ID: NCI-2012-02608
  • SECONDARY ID: ECOG-E1A11
  • SECONDARY ID: E1A11
  • SECONDARY ID: s17-00040
  • SECONDARY ID: E1A11
  • SECONDARY ID: E1A11
  • SECONDARY ID: U10CA180820
  • SECONDARY ID: U10CA021115
  • SECONDARY ID: U24CA196172
  • NCT ID: NCT01863550

Conditions

  • Plasma Cell Myeloma

Interventions

DrugSynonymsArms
Bortezomib[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, VelcadeArm A (bortezomib, lenalidomide, dexamethasone)
CarfilzomibKyprolis, PR-171Arm B (carfilzomib, lenalidomide, dexamethasone)
DexamethasoneAacidexam, 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, VisumetazoneArm A (bortezomib, lenalidomide, dexamethasone)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidArm A (bortezomib, lenalidomide, dexamethasone)

Purpose

This randomized phase III trial studies bortezomib, lenalidomide, and dexamethasone to see how well they work compared to carfilzomib, lenalidomide, and dexamethasone in treating patients with newly diagnosed multiple myeloma. Bortezomib and carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may help the immune system kill abnormal blood cells or cancer cells. Drugs used in chemotherapy, such as dexamethasone, 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. It is not yet known whether bortezomib, lenalidomide, and dexamethasone are more or less effective than carfilzomib, lenalidomide, and dexamethasone in treating patients with multiple myeloma

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare the overall survival between two strategies of lenalidomide maintenance
      following induction with a proteasome inhibitor? immunomodulatory drug (IMiD) combination:
      limited duration of maintenance (24 months) versus indefinite maintenance therapy until
      disease progression.

      II. To compare progression-free survival between bortezomib, lenalidomide, and dexamethasone
      (VRd) and carfilzomib, lenalidomide, and dexamethasone (CRd) induction followed by
      lenalidomide maintenance in patients with newly diagnosed symptomatic multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To compare the progression-free survival between two strategies of lenalidomide
      maintenance following induction with a proteasome inhibitor?IMiD combination: limited
      duration of maintenance (24 months) or indefinite maintenance therapy until disease
      progression.

      II. To compare induction rates of response between VRd and CRd arms. III. To evaluate time to
      progression, duration of response and overall survival between VRd and CRd induction therapy.

      IV. To compare induction rates of toxicity between VRd and CRd arms. V. To evaluate toxicity
      during lenalidomide maintenance. VI. To compare minimal residual disease (MRD) negative rates
      between VRd and CRd arms at end of induction therapy.

      TERTIARY OBJECTIVES:

      I. To compare the short and long-term health-related quality of life impact between the two
      strategies of lenalidomide maintenance.

      II. To compare the impact on health-related quality of life between VRd and CRd induction
      therapy.

      III. To evaluate the association between early induction response and change in
      health-related quality of life.

      IV. To describe changes in health-related quality of life during the induction, active
      maintenance and observation phases.

      V. To evaluate correlation between treatment adherence during maintenance and health-related
      quality of life.

      VI. To compare MRD negative rates between the two strategies of lenalidomide maintenance.

      VII. To compare MRD negative rates between VRd and CRd arms during induction therapy.

      VIII. To examine patterns of change in MRD levels over time and examine conversion from
      detectable to MRD negative status.

      IX. To evaluate agreement and association between International Myeloma Working Group (IMWG)
      and MRD based disease-free status.

      X. To describe the mutational profile of newly diagnosed multiple myeloma. XI. To identify
      mutations associated with resistance to VRd and CRd induction therapy.

      XI. To identify expression profiles associated with MRD negative status with each induction
      therapy.

      XII. To determine the ability of MRD status at induction end to predict short-term and
      long-term overall and progression-free survival.

      XIII. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other
      forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported
      cancer-treatment toxicity (adverse events [both clinical and hematologic] and dose
      modifications).

      XIV. To determine the effects of tobacco on patient-reported physical symptoms and
      psychological symptoms.

      XV. To examine quitting behaviors and behavioral counseling/support and cessation medication
      utilization.

      XVI. To explore the effect of tobacco use and exposure on treatment duration, relative dose
      intensity, and therapeutic benefit.

      OUTLINE:

      INDUCTION: Patients are randomized to 1 of 2 treatment arms.

      ARM A: Patients receive bortezomib subcutaneously (SC) or intravenously (IV) on days 1, 4, 8,
      and 11 of courses 1-8 and days 1 and 8 of courses 9-12; lenalidomide orally (PO) daily on
      days 1-14; and dexamethasone PO daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of courses 1-8 and
      days 1, 2, 8, and 9 of courses 9-12. Treatment repeats every 3 weeks for 12 courses in the
      absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16;
      lenalidomide PO daily on days 1-21; and dexamethasone PO on days 1, 8, 15, and 22. Treatment
      repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable
      toxicity.

      MAINTENANCE: After completion of induction therapy (or completion of at least 6 courses in
      Arm A but stopped early due to unacceptable toxicity, or at least 4 courses in Arm B but
      stopped early due to unacceptable toxicity), patients are then randomized to 1 of 2
      maintenance treatment arms.

      ARM C: Patients receive lenalidomide PO daily on days 1-21. Treatment repeats every 4 weeks
      for 24 courses in the absences of disease progression or unacceptable toxicity.

      ARM D: Patients receive lenalidomide PO daily on days 1-21. Courses repeat every 4 weeks in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years,
      every 6 months for 3 years, and then annually for 10 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (bortezomib, lenalidomide, dexamethasone)ExperimentalPatients receive bortezomib SC or IV on days 1, 4, 8, and 11 of courses 1-8 and days 1 and 8 of courses 9-12; lenalidomide PO daily on days 1-14; and dexamethasone PO daily on days 1, 2, 4, 5, 8, 9, 11, and 12 of courses 1-8 and days 1, 2, 8, and 9 of courses 9-12. Treatment repeats every 3 weeks for 12 courses in the absence of disease progression or unacceptable toxicity.
  • Bortezomib
  • Dexamethasone
  • Lenalidomide
Arm B (carfilzomib, lenalidomide, dexamethasone)ExperimentalPatients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16; lenalidomide PO daily on days 1-21; and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.
  • Carfilzomib
  • Dexamethasone
  • Lenalidomide
Arm C (lenalidomide)ExperimentalPatients receive lenalidomide PO daily on days 1-21. Treatment repeats every 4 weeks for 24 courses in the absences of disease progression or unacceptable toxicity.
  • Lenalidomide
Arm D (lenalidomide)ExperimentalPatients receive lenalidomide PO daily on days 1-21. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  STEP I: Patients must be diagnosed with symptomatic standard-risk multiple myeloma
             (SR-MM) as defined by all of the following (except gene expression profile [GEP]70
             status if unknown):

               -  No evidence of t(14;16) by fluorescence in situ hybridization (FISH) testing on
                  bone marrow or not available

               -  No evidence of t(14:20) by FISH testing on bone marrow or not available

               -  No evidence of deletion 17p by FISH testing on bone marrow

               -  FISH should be from within 90 days of registration

                    -  NOTE: If the FISH result states that no immunoglobulin heavy chain (IgH)
                       abnormality is present, both t(14;16) and t(14;20) can be considered
                       negative; in addition, if the patient has a t(11;14) or t(4;14)
                       translocation present, they can be considered negative for t(14;16) and
                       t(14;20); if testing for t(14;16) or t(14;20) could not be performed for
                       lack of sufficient material or non-availability of the probe in the test
                       panel, patients can be enrolled on the study

               -  Standard Risk GEP70 signature within the past 90 days (only if GEP has been done
                  and results are available)

                    -  NOTE: GEP testing is NOT a requirement for the study; if the test has been
                       done, patients found to have a GEP70 status of high-risk will not be
                       eligible

               -  Serum lactate dehydrogenase (LDH) =< 2 x upper limit of normal (ULN) within the
                  past 28 days

               -  No more than 20% circulating plasma cells on peripheral blood smear differential
                  or 2,000 plasma cells/microliter on white blood cell (WBC) differential of
                  peripheral blood within the past 90 days

                    -  NOTE: This is NOT the plasma cell % from the marrow aspirate

          -  STEP I: Patients must have measurable or evaluable disease as defined by having one or
             more of the following, obtained within 28 days prior to randomization:

               -  >= 1 g/dL monoclonal protein (M-protein) on serum protein electrophoresis

               -  >= 200 mg/24 hours (hrs) 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)

               -  Serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and
                  serum free light chain (FLC) assay are required to be performed within 28 days
                  prior to randomization; 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 I: Hemoglobin >= 8 g/dL (obtained within 28 days prior to randomization)

          -  STEP I: Untransfused platelet count >= 75,000 cells/mm^3 (obtained within 28 days
             prior to randomization)

          -  STEP I: Absolute neutrophil count >= 1000 cells/mm^3 (obtained within 28 days prior to
             randomization)

          -  STEP I: Calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior to
             randomization)

          -  STEP I: Bilirubin =< 1.5 mg/dL (obtained within 28 days prior to randomization)

          -  STEP I: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT])
             and serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])
             < 2.5 times the upper limit of normal (obtained within 28 days prior to randomization)

          -  STEP I: Patients must have received no more than one cycle (4 weeks or less) of prior
             chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of
             prednisone) for treatment of symptomatic myeloma; they should not have been exposed to
             lenalidomide, bortezomib or carfilzomib 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 that meet the study requirements

          -  STEP I: Prior systemic glucocorticoid use for the treatment of non-malignant disorders
             is permitted; prior or concurrent topical or localized glucocorticoid therapy to treat
             non-malignant comorbid disorders is permitted

          -  STEP I: Patients must not have active, uncontrolled seizure disorder; patients must
             have had no seizures in the last 6 months

          -  STEP I: Patients must not have uncontrolled intercurrent illness including
             uncontrolled hypertension, symptomatic congestive heart failure, unstable angina,
             uncontrolled cardiac arrhythmia, uncontrolled psychiatric illness or social situation
             that would limit compliance with the study, or a prior history of Stevens Johnson
             syndrome

          -  STEP I: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
             (performance status [PS] 3 allowed if secondary to pain)

          -  STEP I: Patients with monoclonal gammopathy of undetermined significance or
             asymptomatic multiple myeloma are not eligible

          -  STEP I: Patients must not have grade 2 or higher peripheral neuropathy by Common
             Terminology Criteria for Adverse Events (CTCAE) 4.0

          -  STEP I: Patients must not have active, uncontrolled infection

          -  STEP I: Patients may have a history of current or previous deep vein thrombosis or
             pulmonary embolism but must be willing to take some form of anti-coagulation as
             prophylaxis if they are not currently on full-dose anticoagulation

          -  STEP I: Patients should not have New York Heart Association classification III or IV
             heart failure or myocardial infarction within the previous 6 months

          -  STEP I: Patients with a history of prior malignancy are eligible provided they were
             treated with curative intent and do not require active therapy (currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma ?in situ? of the cervix
             or breast are not excluded)

          -  STEP I: Females of childbearing potential (FCBP)* must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and
             again within 24 hours of starting lenalidomide and must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 28 days before she starts taking lenalidomide throughout the entire
             duration of study treatment, and for 28 days after the last dose of lenalidomide; FCBP
             must also agree to ongoing pregnancy testing; all patients must be counseled at a
             minimum of every 28 days about pregnancy precautions and risks of fetal exposure;
             female subjects must agree to use contraception or abstinence for 30 days after last
             dose of carfilzomib

               -  A female of childbearing potential is any woman, regardless of sexual orientation
                  or whether they have undergone tubal ligation, who meets the following criteria:
                  1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
                  naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
                  at any time in the preceding 24 consecutive months

          -  STEP I: Sexually active males must be willing to use a condom (even if they have
             undergone a prior vasectomy) while having intercourse, while taking lenalidomide and
             for 28 days after stopping lenalidomide; male subjects must also agree to abstain from
             donating blood, semen, or sperm during study participation and for at least 28 days
             after discontinuation from lenalidomide; male subjects must be willing to use condoms
             for 90 days after discontinuation of carfilzomib

          -  STEP I: The following patients will be excluded:

               -  Pregnant women

               -  Nursing women

          -  STEP I: Human immunodeficiency virus (HIV) infection is not excluded; known HIV
             positive patients must meet the following criteria:

               -  Cluster of differentiation (CD)4 cell count >= 350/mm^3

               -  No history of acquired immune deficiency syndrome (AIDS)-related illness

               -  Not currently prescribed zidovudine or stavudine

          -  STEP I: Patient enrolling to this study must agree to register to the mandatory
             RevAssist program, and be willing and able to comply with the requirements of
             RevAssist

          -  STEP II: Patients must have complete induction without experiencing progression or
             patients must have received at least 6 cycles on Arm A and 4 cycles on Arm B but
             stopped induction therapy due to adverse events

          -  STEP II: Step 2 registration must be within 6 weeks of completing step 1 therapy

          -  STEP II: Patients must not have received any non-protocol therapy outside of the
             assigned induction therapy including stem cell transplant

          -  STEP II: ECOG performance status 0, 1, or 2 (PS 3 allowed if secondary to pain)

          -  STEP II: Any adverse event related to step 1 therapy must have resolved to grade 2 or
             less

          -  STEP II: Hemoglobin >= 8 g/dL (within 28 days prior to randomization to Step II)

          -  STEP II: Platelet count >= 75,000 cells/mm^3 (within 28 days prior to randomization to
             Step II)

          -  STEP II: Absolute neutrophil count >= 1000 cells/mm^3 (within 28 days prior to
             randomization to Step II)

          -  STEP II: Calculated creatinine clearance >= 30 mL/min (within 28 days prior to
             randomization to Step II)

          -  STEP II: Bilirubin =< 1.5 mg/dL (within 28 days prior to randomization to Step II)

          -  STEP II: SGPT (ALT) and SGOT (AST) < 2.5 times the upper limit of normal (within 28
             days prior to randomization to Step II)

          -  STEP II: Females of childbearing potential (FCBP)* must have a negative serum or urine
             pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and
             again within 24 hours of starting lenalidomide and must either commit to continued
             abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
             control, one highly effective method and one additional effective method AT THE SAME
             TIME, at least 28 days before she starts taking lenalidomide throughout the entire
             duration of study treatment, and for 28 days after the last dose of lenalidomide; FCBP
             must also agree to ongoing pregnancy testing; all patients must be counseled at a
             minimum of every 28 days about pregnancy precautions and risks of fetal exposure

               -  A female of childbearing potential is any woman, regardless of sexual orientation
                  or whether they have undergone tubal ligation, who meets the following criteria:
                  1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
                  naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
                  at any time in the preceding 24 consecutive months

          -  STEP II: Sexually active males must be willing to use a condom (even if they have
             undergone a prior vasectomy) while having intercourse, while taking lenalidomide and
             for 28 days after stopping lenalidomide; male subjects must also agree to abstain from
             donating blood, semen, or sperm during study participation and for at least 28 days
             after discontinuation from lenalidomide; males must agree to use contraception and
             agree to not donate sperm for at least 90 days after the last day of carfilzomib

          -  STEP II: The following patients will be excluded:

               -  Pregnant women

               -  Nursing women

          -  STEP II: Patient enrolling to this study must agree to register to the mandatory
             RevAssist program and be willing and able to comply with the requirements of RevAssist
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS) for the maintenance analysis
Time Frame:From the maintenance randomization to death due to any cause or, censored at the date last known alive, assessed up to 15 years
Safety Issue:
Description:The Kaplan-Meier (KM) method will be used to describe the overall survival function by arm. Sensitivity analysis will be done to evaluate OS in the subset of eligible patients and censoring patients at time of non-protocol therapy.

Secondary Outcome Measures

Measure:Progression-free survival for the maintenance analysis
Time Frame:From the maintenance randomization until the earlier of progression or death due to any cause, assessed up to 15 years
Safety Issue:
Description:Weighted Cox regression will be used.
Measure:Overall survival for the induction analysis
Time Frame:From induction randomization to death due to any cause, or censored at the date last known alive, assessed up to 15 years
Safety Issue:
Description:The KM method will be used.
Measure:Response rates including partial response (PR), very good partial response (VGPR), immunofixation negative complete response (IF-CR) and complete response (CR)
Time Frame:At 2.8 months
Safety Issue:
Description:Will be compared between induction arms using Fisher?s exact test.
Measure:Response rates including PR, VGPR, IF-CR and CR
Time Frame:At 8.3 months
Safety Issue:
Description:Will be compared between induction arms using Fisher?s exact test.
Measure:Time to progression (TTP) for the induction analysis
Time Frame:From the induction randomization to progression, or censored at the date of last disease evaluation for those without progression reported, assessed up to 15 years
Safety Issue:
Description:TTP distributions will be estimated by induction arm using Kaplan-Meier methods.
Measure:Duration of response (DOR) for the induction analysis
Time Frame:From first objective response (partial response or better) since induction randomization until the earlier of progression or death due to any cause, or censored at date of last disease evaluation for those without events reported, assessed up to 15 years
Safety Issue:
Description:Duration of response will be estimated using Kaplan-Meier methods in the subset of patients achieving partial response or better while on induction therapy.
Measure:Incidence of overall grade 3 or higher non-hematologic toxicity and grade 3 or higher toxicity by type during induction, active maintenance and observation phases using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame:Up to 15 years
Safety Issue:
Description:Fisher?s exact test will be used.
Measure:Incidence of grade 2 or higher peripheral neuropathy and cardiac toxicity during induction phase assessed using CTCAE version 5.0
Time Frame:Up to 36 weeks
Safety Issue:
Description:Fisher?s exact test will be used.
Measure:Minimal residual disease (MRD) negative rates
Time Frame:At 8.3 months after induction randomization
Safety Issue:
Description:MRD evaluation by multiparametric flow cytometry will be conducted and patients classified as MRD negative, MRD positive or not evaluable. At each time point, MRD negative rates with two-sided 95% exact confidence intervals on each arm will be estimated. Patterns of change over time in MRD will also be evaluated using longitudinal regression analysis with general linear mixed effects models and GEE semi-parametric models. MRD negative rates will be compared between either induction or maintenance arms depending on the assessment time point using the Mantel-Haenszel test stratified either on intent to transplant at progression or induction arm (Step 1 and 2 stratification factors, respectively).
Measure:Change in the Functional Assessment of Cancer Therapy-Neurotoxicity Trial Outcome Index (FACT-Ntx TOI) for the transition to maintenance analysis
Time Frame:From week 36 (the end) of induction therapy to week 24 (end of course 6) of maintenance therapy
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Change in the FACT-Ntx TOI for the short-term maintenance analysis
Time Frame:From the end of 2 years of maintenance to 3 years post maintenance randomization
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Change in the FACT-Ntx TOI for the long-term maintenance analysis
Time Frame:From the end of 2 years of maintenance to 5 years post maintenance randomization
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Change in the FACT-Ntx TOI for the end of induction analysis
Time Frame:From baseline (induction randomization) to 36 weeks (end) of induction therapy
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Change in the FACT-Ntx TOI for the early induction analysis
Time Frame:From baseline (induction randomization) to 2.8 months of induction therapy
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Levels and changes in the FACT-Ntx TOI and Functional Assessment of Cancer Therapy- Multiple Myeloma (FACT-MM) during induction, active maintenance and observation phases
Time Frame:Up to 15 years
Safety Issue:
Description:Will be analyzed using linear mixed models.
Measure:Time to worsening of FACT-Ntx TOI for the induction analysis
Time Frame:From the baseline assessment at induction randomization to a decrease of 7 points, assessed up to 15 years
Safety Issue:
Description:Will be analyzed with KM methods and Cox regression.
Measure:Time to worsening of FACT-MM for the maintenance analysis
Time Frame:From the baseline assessment at maintenance randomization to a decrease of 4 points, assessed up to 15 years
Safety Issue:
Description:Will be analyzed with KM methods and Cox regression.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ECOG-ACRIN Cancer Research Group

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