Overview

This trial is active, not recruiting.

Condition myeloma
Treatments lenalidomide, bortezomib
Phase phase 3
Sponsor University Hospital, Toulouse
Collaborator Dana-Farber Cancer Institute
Start date October 2010
End date September 2018
Trial size 700 participants
Trial identifier NCT01191060, 09 110 01

Summary

Objective of this study is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs Progression-free survival (by at least 9 months).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent) Autologous stem cell transplant: Melphalan: infused over two days (day -2 and day -1) or as a single infusion (day-2) according to institutional practice Re-infusion of PBSCs RVD q 21 days (2 cycles) Maintenance Lenalidomide q28 days (12 months)
lenalidomide, bortezomib Lenalidomide (REVLIMID®)
Lenalidomide Bortezomib Dexamethasone cycles: Number of cycles: 5 cycles for arm B Cycle length Dosage: Lenalidomide: 25 mg/day on days 1-14 of each cycle Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle Maintenance phase (12 months): Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed
(Experimental)
RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent) RVD q 21 days (5 cycles) Maintenance Lenalidomide q28 days (12 months)
lenalidomide, bortezomib Lenalidomide (REVLIMID®)
Lenalidomide/Bortézomib/Dexamethasone cycles: Number of cycles: 8 cycles for arm A Cycle length Dosage: Lenalidomide: 25 mg/day on days 1-14 of each cycle Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle Maintenance phase (12 months): Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

Primary Outcomes

Measure
Progression Free Survival
time frame: up to 4 years

Secondary Outcomes

Measure
Response Rates
time frame: up to 4 years
Time To Progression
time frame: up to 4 years
Toxicity comparison
time frame: up to 4 years
Genetic prognostic groups definition
time frame: up to 4 years
Best treatment examination in each GEP-defined prognostic group.
time frame: up to 4 years

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

Inclusion Criteria for registration : (with labs performed within 21 days of initiation of protocol therapy): - Patients diagnosed with multiple myeloma based on International Myeloma Foundation 2003 Diagnostic Criteria. - Patients must have symptomatic myeloma with myeloma-related organ damage. - Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains. - Age between 18 and 65 years at the time of signing the informed consent document. - ECOG performance status <2 (Karnofsky ≥ 60%) - Negative HIV blood test Exclusion Criteria for registration (section 4.2): - Participants must not have been treated with any prior systemic therapy for multiple myeloma. Treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and initiation of protocol therapy entry in the study is observed. Similarly, the dose of corticosteroids received by the participant should not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol therapy. - Primary amyloidosis (AL) or myeloma complicated by amylosis. - Participants may not be receiving any other study investigational agents. - Participants with known brain metastases - Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to study agents - Platelet count < 50,000/mm3 per µLwithin 21 days of initiation of protocol therapy. Transfusion within 7 days of screening is not allowed to meet platelet eligibility criteria. - ANC < 1,000 cells/mm3 within 21 days of initiation of protocol therapy. Growth factor within 7 days of screening is not allowed to meet ANC eligibility criteria. - Hemoglobin < 8.0 g/dL within 21 days of initiation of protocol therapy. Transfusion may be used to meet hemoglobin eligibility criteria. - Hepatic impairment, defined a bilirubin > 1.5 x institutional upper limit of normal (ULN) > 2 mg/dL (Patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible) and or AST (SGOT), or ALT (SGPT), or alkaline phosphatase > 2 x ULN - Renal insufficiency, defined as serum creatinine > 2.5 mg/dl and/or creatinine clearance < <40 60 ml/min (actual or calculated). The Cockgroft-Gault formula should be used for calculating creatinine clearance values, and may be located in Section 4.2 - Respiratory compromise, defined as ventilation tests and with DLCO < 50% - Participant must not demonstrate with clinical signs of heart or coronary failure, or evidence of LVEF < 40%. Participant must not have with myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA Appendix VII) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant. - Intercurrent illness including, but not limited to ongoing or active severe infection, known (active or not) infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements. - Participant with previous history of another malignant condition, except for basal cell carcinoma and stage I cervical cancer - Female participant who is pregnant or breast-feeding - Inability to comply with an anti-thrombotic treatment regimen - Peripheral neuropathy ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days of initiation of protocol therapy - Mental illness likely to interfere with participation in the study and Adults under juridical protection

Additional Information

Official title Randomized Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone to High-Dose Treatment With ASCT in the Initial Management of Myeloma in Patients up to 65 Years of Age
Principal investigator MICHEL ATTAL, MD PhD
Description Study design Phase III, multicenter, randomized, open-label study designed to evaluate the clinical benefit from the drug combination RVD without immediate high-dose therapy (HDT) followed by lenalidomide maintenance (Arm A) versus RVD plus HDT and PBSCT followed by lenalidomide maintenance (Arm B).
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by University Hospital, Toulouse.