A Randomized Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone (RVD) to High-Dose Treatment with Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients up to 65 Years of Age (IFM/DFCI 2009) - IFM/DFCI 2009

Phase 1

• Conditions: Myeloma, Multiple Myeloma; MedDRA version: 12.0Level: LLTClassification code 10028228Term: Multiple myeloma; MedDRA version: 12.0Level: LLTClassification code 10028566Term: Myeloma

• Registration Number: EUCTR2009-016871-32-FR
• Lead Sponsor: CHU de TOULOUSE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03-30
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

Eligibility Criteria for registration
•Participants must have a diagnosis of MM, according to International Myeloma Foundation 2003 Diagnostic Criteria. According to these criteria, all three of the following must be met with labs peformed within 21 days of study entry:
?Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma
?Monoclonal protein (M-protein) present in the serum and/or urine. If no monoclonal protein is detected (non-secretory) disease, then > 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required
?Myeloma-related organ dysfunction (1 or more) of the following. A variety of other types of end-organ dysfunctions can occasionally occur and lead to a need for therapy.
?[C] Calcium elevation in the blood, defined as serum calcium > 10.5 mg/l or upper limit of normal
?[R] Renal insufficiency, defined as serum creatinine > 2 mg/dl
?[A] Anemia, defined as hemoglobin <10 g/dl or 2 g < normal
?[B] Lytic bone lesions or osteoporosis. If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the sole defining criteria, then > 30% plasma cells are required in the bone marrow.
?Note: These criteria identify Stage IB and Stages II and III A/B myeloma by Durie-Salmon stage. Stage IA becomes smoldering or indolent myeloma.
•Participants must have symptomatic myeloma with organ damage related to myeloma as defined in section 3.1.1 with labs done within 21 days of study entry.
•Participants must have myeloma that is measurable by either serum evaluation of the monoclonal component or by assay of free light chains (serum or urinary). Measurable disease is defined as one or more of the following: serum M-protein > 1 g/dl, urine M-protein > 200 mg/24 h, and/or serum FLC assay: involved FLC level > 10 mg/dl provided serum FLC ratio is abnormal.
•Age between 18 and 65 years at the time of signing the informed consent form.
•ECOG performance status <2 (Karnofsky >60%, see Appendix V).
•Negative HIV blood test within 21 days of study entry. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for PK interactions with lenalidomide, bortezomib and/or dexamethasone. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.

oCriteria for women of non-childbearing potential
A female subject or a female partner of a male subject is considered to have childbearing potential unless she meets at least one of the following criteria:
•Age = 50 years and naturally amenorrhoeic for = 1 year*
•Premature ovarian failure confirmed by a specialist gynaecologist
•Previous bilateral salpingo-oophorectomy, or hysterectomy
•XY genotype, Turner syndrome, uterine agenesis.
*Amenorrhoea following cancer therapy does not rule out childbearing potential.

Female subjects of childbearing potential must follow the recommandations as precognized in the protocol.

Male subjects must
-Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
-Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
All subjects must
-Agr

Exclusion Criteria

All labs should be done within 21 days of study entry.
•Participant must not have been treated with any prior systemic therapy. Treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and entry in the study is observed. Similarly, the dose of corticosteroids received by the participant prior to study entry as part of any initial therapy should not exceed the equivalent of 160 mg of dexamethasone over a two-week period.
•Primary amyloidosis (AL) or myeloma complicated by amylosis.
•Participants may not be receiving any other study agents.
•Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
•Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to lenalidomide, bortezomib and/or dexamethasone.
•Participants with platelet level <50,000/uL. Transfusion may not be used to meet platelet eligibility criteria
•Participants with an absolute neutrophil count (ANC) <1000/uL. Growth factor may not be used to meet ANC eligibility criteria.
•Participants with hemoglobin level < 8.0 g/dL. Transfusion may be used to meet hemoglobin eligibility criteria.
•Hepatic impairment, defined as bilirubin > 2mg/dL and AST (SGOT), ALT (SGPT), or alkaline phosphotase > 2x ULN
•Renal insufficiency, defined as serum creatinine> 2.5 mg/dL and/or creatinine clearance < 40 mL/min (either actual or calculated values may be used)
•Respiratory compromise, defined as ventilation tests and DLCO < 50% normal
•Participant must not demonstrate clinical signs of heart or coronary failure, or evidence of left ventricular ejection fraction (LVEF) < 40%. Participant must not have myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conductive system abnormalities.
•Intercurrent illness including, but not limited to ongoing or active severe infection, known infection with hepatitis B or C virus, poorly controlled diabetes, or psychiatric illness/social situations that would limit compliance with study requirements.
•Participants may not have previous history of another malignant condition except for basal cell carcinoma and stage I cervical cancer.
•Female participants must not be pregnant or breast-feeding. Pregnant women are excluded from this study because lenalidomide is an immunomodulatory agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with lenalidomide, breastfeeding should be discontinued if the mother is treated with lenalidomide. These potential risks may also apply to other agents used in this study.
•Inability to comply with an anti-thrombotic treatment regimen (e.g., aspirin, Lovenox administration)
•Peripheral neuropathy > Grade 2 on clinical examination.
•Mental illness likely to interfere with participation in the study and adults under juridical protection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified