Study to Determine Efficacy and Safety of Lenalidomide Plus Low-dose Dexamethasone Versus Melphalan, Prednisone, Thalidomide in Patients With Previously Untreated Multiple Myeloma (FIRST)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT00689936
First received: June 2, 2008
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide and low-dose dexamethasone
Drug: Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
Drug: Melphalan, Prednisone and Thalidomide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Open-label, 3-arm Study to Determine the Efficacy and Safety of Lenalidomide(REVLIMID) Plus Low-dose Dexamethasone When Given Until Progressive Disease or for 18 Four-week Cycles Versus the Combination of Melphalan, Prednisone, and Thalidomide Given for 12 Six-week Cycles in Patients With Previously Untreated Multiple Myeloma Who Are Either 65 Years of Age or Older or Not Candidates for Stem Cell Transplantation.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Time from randomization to the first documentation of disease progression.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Time from randomization to death due to any cause

  • Response (complete response [CR], very good partial response [VGPR], partial response [PR], and overall response [CR + VGPR + PR]) [ Time Frame: Cycle 2 day 1 to Study Discontinuation,; Up to 430 weeks ] [ Designated as safety issue: No ]
    Response is defined according to the International Myeloma Working Group (IMWG) Response Criteria (Durie, 2006).

  • Duration of response [ Time Frame: Cycle 2 day 1 to Study Discontinuation: Up to 430 weeks ] [ Designated as safety issue: No ]
    Duration of response for subjects last known to be alive with no progression after a CR or VGPR or PR

  • Time to response [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    The time to myeloma response is defined as the time from randomization to the time the response criteria for CR or VGPR or PR are first met.

  • Safety (adverse events [type, frequency, and severity of AEs, and relationship of AEs to study drug], laboratory abnormalities, and hospitalizations) [ Time Frame: Up to 436 weeks and within 28 days after the last dose of the last study drug received. ] [ Designated as safety issue: Yes ]
    Number of patients with adverse events and relationship of adverse events to study drug, laboratory abnormalities, and hospitalizations.

  • Time to treatment failure (TTF) [ Time Frame: to 436 weeks ] [ Designated as safety issue: No ]
    Time to treatment failure (TTF) will be calculated as the time between the randomization and discontinuation of study treatment for any reason

  • Time to second-line anti-myeloma treatment [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Time to second-line anti-myeloma therapy is defined as time from randomization to the start of another non-protocol anti-myeloma therapy.

  • Best response achieved to second-line anti-myeloma treatment [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Best response achieved to second-line anti-myeloma therapy.

  • Relationship of cytogenetic findings in the malignant myeloma clone at baseline to clinical outcomes [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Subgroup analysis for each clinical endpoint above.

  • Quality of life (QOL) [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    European Organization for Research and Treatment of Cancer QOL Questionnaire for Patients with Cancer (EORTC QLQ-C30) and QLQ for Patients with Multiple Myeloma (QLQ-MY20) Module and the descriptive system of the EQ-5D.

  • Pharmacoeconomic / clinical benefit [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    Pharmacoeconomic data will be analyzed to characterize usage of health services, concomitant medication use, and onset of co-morbidities (e.g., treatment emergent adverse events, lab abnormalities) in the three study arms.

  • Assess improvement in CRAB criteria [ Time Frame: Up to 436 weeks ] [ Designated as safety issue: No ]
    The improvement in CRAB criteria will be assessed for subjects with available data (renal function, hematology and Neutrophil).


Enrollment: 1623
Study Start Date: August 2008
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide / Dexamethasone until disease progression
Lenalidomide plus low-dose dexamethasone given until disease progression
Drug: Lenalidomide and low-dose dexamethasone

Lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg 20mg, or 25 mg capsules ,given either days 1-21 of each 28 day cycles or given every other day for 21 days until documentation of PD.

Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle up to disease progression

Other Name: Revlamid
Experimental: Lenalidomide / Dexamethasone for 18 cycles
Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles
Drug: Lenalidomide plus low-dose dexamethasone given for 18 four-week cycles

lenalidomide - oral, 2.5mg, 5mg, 10mg, 15mg, 20 mg or 25 mg capsules given on days 1-21 of each 28 day cycle or every other day for 21 days for 18 cycles.

Dexamethasone - oral 4mg tablets for a total dose of 20mg or 40 mg given days 1,8,15 and 22 of each 28 day cycle for 18 cycles

Other Name: revlidmid
Active Comparator: Melphalan, Prednisone, and Thalidomide (MPT) for 12 cycles
Combination of Melphalan, Prednisone and Thalidomide given for 12 six-week cycles
Drug: Melphalan, Prednisone and Thalidomide
Melphalan - oral, 2mg tablets dosed at either 0.25mg/kg, 0.125 mg/kg, 0.20mg/kg or 0.10mg/kg on days 1-4 of each 42 day cycle up to 12 cycles Prednisone - oral, 5mg, 10mg, 20 mg and 50 mg tablets dosed at 2mg/kg daily days 1-4 of each 42 day cycle for up to 12 cycles Thalidomide - oral, 50mg, 100mg and 200 mg capsules dosed at either 100mg or 200 mg daily on days 1-41 of each 42 day cycle for up to 12 cycles
Other Names:
  • Prednisone
  • Thalomid

Detailed Description:

CC-5013-MM020/IFM 07-01 is a Phase III, multicenter, randomized, open-label, 3-arm study that will compare the efficacy and safety of two Lenalidomide plus low-dose dexamethasone regimens given for two different durations of time (i.e., until progressive disease [PD] or for up to a maximum of 18 four-week cycles) to that of MPT given for a maximum of 12 six-week cycles.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must understand and voluntarily sign informed consent form
  2. Age ≥ 18 years at the time of signing consent
  3. 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 <10 g/dl or 2 g < laboratory normal) [B] Lytic bone lesions or osteoporosis

    AND have measurable disease by protein electrophoresis analyses as defined by the following:

    • IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
    • IgA multiple myeloma: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥ 200 mg/24 hours
    • IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200mg/24hours
    • IgD multiple myeloma: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level ≥ 200 mg/24 hours
    • Light chain multiple myeloma: Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours

    AND are at least 65 years of age or older or, if younger than 65 years of age, are not candidates for stem cell transplantation because:

    • The patient declines to undergo stem cell transplantation or
    • Stem cell transplantation is not available to the patient due to cost or other reasons
  4. ECOG performance status of 0, 1, or 2
  5. Able to adhere to the study visit schedule and other protocol requirements
  6. Females of child-bearing potential (FCBP)^2:

    1. Must agree to undergo two medically supervised pregnancy tests prior to starting study therapy with either Rd or MPT. The first pregnancy test will be performed within 10-14 days prior to the start of Rd or MPT and the second pregnancy test will be performed within 24 hours prior to the start of Rd or MPT. She must also agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. This applies even if the patient practices complete and continued sexual abstinence.
    2. Must commit to either continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy.
  7. Male Patients:

    1. Must agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy.
    2. Must agree to not donate semen during study drug therapy and for a period after end of study drug therapy.
    3. Must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy.
  8. All patients must:

    1. Have an understanding that the study drug could have a potential teratogenic risk.
    2. Agree to abstain from donating blood while taking study drug therapy and following discontinuation of study drug therapy.
    3. Agree not to share study medication with another person. All FCBP and male patients must be counseled about pregnancy precautions and risks of fetal exposure.

Exclusion Criteria:

  1. Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of randomization]).
  2. Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, patient with unstable cardiac disease as defined by: Cardiac events such as MI within the past 6 months, NYHA heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; patients with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
  3. Pregnant or lactating females.
  4. Any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1,000/µL (1.0 x 109/L)
    • Untransfused platelet count < 50,000 cells/µL (50 x 10^9/L)
    • Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN)
  5. Renal failure requiring hemodialysis or peritoneal dialysis.
  6. 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)
  7. Patients who are unable or unwilling to undergo antithrombotic therapy.
  8. Peripheral neuropathy of > grade 2 severity.
  9. 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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00689936

  Show 281 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Christian Jacques, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT00689936     History of Changes
Other Study ID Numbers: CC-5013-MM-020, 2007-004823-39
Study First Received: June 2, 2008
Last Updated: August 26, 2013
Health Authority: Austria: Agency for Health and Food Safety
Canada: Health Canada
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
Italy: The Italian Medicines Agency
Portugal: National Pharmacy and Medicines Institute
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe
Taiwan: Department of Health
South Korea: Korea Food and Drug Administration (KFDA)
Belgium: Federal Agency for Medicinal Products and Health Products
Greece: National Organization of Medicines
China: Food and Drug Administration

Keywords provided by Celgene Corporation:
newly diagnosed multiple myeloma
Lenalidomide
Revlimid
phase III

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Prednisone
Dexamethasone 21-phosphate
Lenalidomide
Melphalan
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014