Phase 3
Completed N=1,623
Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma
Source: ClinicalTrials.gov NCT00689936 ↗Enrolled (actual)
1,623
Serious AEs
59.3%
Results posted
Aug 2017
Primary outcomePrimary: Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC) — 25.5; 20.7; 21.2 months — p=0.00006
◆ Published Evidence
Highly cited
270citations · ~30 / year
Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.
Summary
The purpose of this study is to compare the safety and efficacy of Lenalidomide plus low dose dexamethasone to that of the combination of melphalan, prednisone and thalidomide.
Linked Publications (5)
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Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.
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Continuous treatment with lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma in Asia: subanalysis of the FIRST trial.
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Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.
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Updated Outcomes and Impact of Age With Lenalidomide and Low-Dose Dexamethasone or Melphalan, Prednisone, and Thalidomide in the Randomized, Phase III FIRST Trial.
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Impact of renal impairment on outcomes with lenalidomide and dexamethasone treatment in the FIRST trial, a randomized, open-label phase 3 trial in transplant-ineligible patients with multiple myeloma.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Kaplan-Meier Estimates of Progression-free Survival (PFS) Based on the Response Assessment by the Independent Review Adjudication Committee (IRAC) |
25.5; 20.7; 21.2 | 0.00006 sig |
| PRIMARY Kaplan-Meier Estimates of PFS Based on the Response Assessment by the Investigator At the Time of Final Analysis |
26.0; 21.0; 21.9 | <0.00001 sig |
| SECONDARY Kaplan Meier Estimates of Overall Survival at the Time of Final Analysis (OS) |
59.1; 62.3; 49.1 | 0.00234 sig |
| SECONDARY Percentage of Participants With an Objective Response Based on IRAC Review |
75.1; 73.4; 62.3 | <0.00001 sig |
| SECONDARY Percentage of Participants With an Objective Response Based on Investigator Assessment at Time of Final Analysis |
80.7; 78.6; 67.5 | <0.00001 sig |
| SECONDARY Kaplan Meier Estimates of Duration of Myeloma Response as Determined by the IRAC |
35.0; 22.1; 22.3 | <0.00001 sig |
| SECONDARY Kaplan Meier Estimates of Duration of Myeloma Response as Determined by an Investigator Assessment at Time of Final Analysis |
31.5; 21.5; 22.1 | <0.00001 sig |
| SECONDARY Time to First Response Based on the Review by the IRAC |
1.8; 1.8; 2.8 | <0.00001 sig |
| SECONDARY Time to First Response Based on the Investigator Assessment at the Time of Final Analysis |
1.8; 1.8; 2.8 | <0.00001 sig |
| SECONDARY Kaplan Meier Estimates of Time to Treatment Failure (TTF) |
16.9; 17.2; 14.1 | 0.00012 sig |
| SECONDARY Kaplan Meier Estimates of Time to Treatment Failure (TTF) at the Time of Final Analysis |
16.9; 17.2; 14.1 | 0.00002 sig |
| SECONDARY Kaplan Meier Estimates for Time to Second-line Anti-myeloma Treatment (AMT) |
39.1; 28.5; 26.7 | <0.00001 sig |
| SECONDARY Kaplan Meier Estimates of Time to Second Line Therapy AMT at the Time of Final Analysis |
36.7; 28.5; 26.7 | <0.00001 sig |
| SECONDARY Percentage of Participants With an Objective Response After Second-line Anti-myeloma Treatment at the Time of Final Analysis |
46.2; 53.1; 45.7 | 0.93824 |
| SECONDARY Percentage of Participants With a Myeloma Response by Adverse Risk Cytogenetic Risk Category Based on IRAC Review. |
70.0; 69.7; 58.2 | 0.02134 sig |
| SECONDARY Percentage of Participants With a Myeloma Response by Favorable Hyperdiploidy Risk Cytogenetic Risk Category Based on IRAC Review |
80.4; 81.6; 70.6 | 0.11152 |
| SECONDARY Percentage of Participants With a Myeloma Response by Normal Risk Cytogenetic Risk Category Based on IRAC Review |
80.4; 74.8; 61.0 | 0.00043 sig |
| SECONDARY Percentage of Participants With a Myeloma Response by Uncertain Risk Cytogenetic Risk Category Based on IRAC Review |
60.5; 76.8; 57.5 | 0.82128 |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain |
0.4; -1.3; 1.0; 4.8; 4.7; 4.3 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain |
-1.7; -1.4; -0.9; 3.4; 4.7; 2.2 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Role Functioning Domain |
-2.7; -4.6; -2.4; 2.4; 6.3; 4.1 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain |
0.6; 0.1; 1.0; 3.8; 3.9; 2.1 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Cognitive Functioning Domain |
-1.2; -1.7; -1.8; -0.7; 1.8; -1.5 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Social Functioning Domain |
-4.3; -2.2; -1.4; 0.7; 2.0; 2.4 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Fatigue Domain |
2.6; 4.4; 2.8; -2.5; -3.4; -1.8 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Pain Domain |
-5.4; -4.4; -7.8; -13.4; -13.1; -12.1 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Nausea/Vomiting Domain |
1.8; -0.5; 4.0; -1.1; -2.5; -1.2 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Dyspnea Domain |
0.9; 3.6; 4.2; -0.8; -1.9; 2.0 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Insomnia Domain |
2.1; 3.2; -10.5; 0.2; -1.3; -8.9 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Appetite Loss Domain |
1.3; 2.9; 1.0; -5.9; -3.3; -6.2 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Constipation Domain |
8.3; 6.3; 18.4; 1.8; 0.0; 13.9 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Diarrhea Domain |
3.8; 2.3; -0.6; 3.7; 3.4; -2.4 | — |
| SECONDARY Change From Baseline in the EORTC QLQ-C30 Financial Difficulties Domain |
2.1; -0.3; 0.5; 1.9; -0.4; 1.9 | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms Scale |
-4.0; -4.1; -4.4; -9.1; -10.0; -7.0 | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Side Effects Treatment Scale |
2.5; 4.0; 5.6; 1.0; 1.2; 3.5 | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Future Perspective Scale |
4.7; 3.9; 3.3; 8.5; 9.2; 6.3 | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Body Image Scale |
-4.5; -1.5; -1.6; -1.7; 0.8; -3.0 | — |
| SECONDARY Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Health Utility Index Score |
0.0; -0.0; 0.0; 0.1; 0.1; 0.1 | — |
| SECONDARY Healthcare Resource Utilization (HRU): Rate of Inpatient Hospitalizations Per Year |
— | — |
| SECONDARY Number of Participants With Adverse Events (AEs) During the Active Treatment Phase |
529; 536; 539; 453; 433; 480 | — |
| SECONDARY Shift From Baseline to Most Extreme Postbaseline Value in Creatinine Clearance (CrCl) During the Active Treatment Phase |
15; 17; 19; 18; 14; 19 | — |
| SECONDARY Shift From Baseline to Most Extreme Postbaseline Value in Absolute Neutrophil Count During the Active Treatment Phase |
103; 133; 37; 96; 85; 79 | — |
| SECONDARY Shift From Baseline to Most Extreme Postbaseline Value in Hemoglobin During the Active Treatment Phase |
6; 10; 9; 39; 30; 25 | — |
| SECONDARY Shift From Baseline to Most Extreme Postbaseline Value in Platelet Count During the Active Treatment Phase. |
197; 197; 165; 216; 211; 208 | — |
| SECONDARY Improvement of Infection Rate by Observing the Historical Data Compared to the Clinical Data Base |
— | — |
Eligibility Criteria
Inclusion Criteria
- Must understand and voluntarily sign informed consent form
- Age ≥ 18 years at the time of signing consent
- Previously untreated, symptomatic multiple myeloma as defined by the 3 criteria below:
- MM diagnostic criteria (all 3 required):
- Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma
- Monoclonal protein present in the serum and/or urine
- Myeloma-related organ dysfunction (at least one of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/dl or upper limit of normal) [R] Renal insufficiency (serum creatinine >2 mg/dl) [A] Anemia (hemoglobin 3.0 x upper limit of normal (ULN)
- Renal failure requiring hemodialysis or peritoneal dialysis.
- Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histological finding of prostate cancer (TNM stage of T1a or T1b)
- Patients who are unable or unwilling to undergo antithrombotic therapy.
- Peripheral neuropathy of > grade 2 severity.
- Known HIV positivity or active infectious hepatitis, type A, B, or C. Primary AL (immunoglobulin light chain) amyloidosis and myeloma complicated by amyloidosis.
- 1 A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma-related.
- 2 A FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (i.e., 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).
Data sourced from ClinicalTrials.gov (NCT00689936) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.