Induction and Consolidation With Elotuzumab Before and After Peripheral Stem Cell Autologous Graft in Elderly Patients With Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria
研究概览
简要总结
This is a multicenter, open-label phase II study, assessing the efficacy of elotuzumab in elderly patients with multiple myeloma undergoing peripheral stem cell autologous graft
详细描述
In patients of 65 years of age or older, intensive treatment (TI) with hematopoietic stem cell autologous graft (ASCH) is not considered as the gold standard. Nowadays, given the rise of new treatments, new studies assessing TI with ASCH in elderly, seem required. The association bortezomib (VEL) - thalidomide (THAL) - dexamethasone (DEX) is considered as the standard induction (Kumar, Flinn et al. 2012, Ludwig, Viterbo et al. 2013). However, more and more strategies with immunotherapies are developed. Furthermore, it looks encouraging to use several monoclonal antibodies at different clinical development levels. Thus, elotuzumab (ELO) is an IgG1 (immunoglobulin gamma-1) (IgGκ) humanized monoclonal antibody directed against SLAMF7. SLAMF7 is a glycoprotein expressed by myeloma cells and natural killer (NK) but not by healthy tissues. Consequently, elotuzumab can kill specifically myeloma cells without affecting healthy tissues (Hsi, Steinle et al. 2008). A phase I study assessed the safety of ELO in association with VEL, REV (Lenalidomide) and DEX in induction first-line treatment in elderly patients with median age of 67 years (Usmani, Sexton et al. 2015). There were no significant increase of side effects with this association compared with side effects usually reported with VEL, REV and DEX. Thus, adding ELO could lead to an increase of response rate, with no increase of toxicity.
For more than 10 years, the standard intensive treatment associates a MEL (MELPHALAN) conditioning (200 mg/m2) with a blood graft. In a recent study, almost all patients aged between 65-69 and 70-74 years received MEL at 200 mg/m2. The adverse events rate was similar between the different ages and a very low non-tied relapse mortality. Thus, in elderly patients selected, the use of MEL at 200 mg/m2 seems sure.
Moreover, it's widely admitted that the conditioning treatment should be based on an efficient drugs association with a limited toxicity. Studies assessing consolidation treatment with an association of new drugs are limited. Initial results suggest that the use of new drugs after intensive treatment (IT) with ASCH should increase response rate and improve progression-free survival and global survival.
The aim of this study IFM 2016-03 is to assess intensive treatment (IT) with AHSCT (Autologous hematopoietic stem cell transplantation) in elderly and to associate the different steps (induction, high dose conditioning, consolidation) with immunotherapy. Given the prior results of IFM and international studies, a VGPR (Very Good Partial Response) rate of around 85% is expected.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 66 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Multiple myeloma de novo.
- •Stage DS (Durie-Salmon) : III, II, I with at least 1 symptomatic bone lesion (confirmed by radiology).
- •Age > 65 years
- •Indication for a first line treatment with induction, stem cell autologous graft and consolidation
- •Available documentation including cytogenetic and International Staging System (ISS) of the initial diagnosis before inclusion,
- •Effective contraceptive method for men with a partner of childbearing age during all the treatment period and within 6 months after the last cure
- •Affiliated to social security
- •Written informed consent
- •Willingness and ability to respect the visits and all the demands required by the study
- •Patient eligible to a high dose chemotherapy and fulfilling the following biological criteria :
- •Neutrophils ≥ 1,0 × 109/L
- •Platelets ≥ 75 ×109/L (platelets transfusions are not allowed within 3 days before inclusion)
- •Total bilirubin ≤ 1,5 × upper limit.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit
- •Creatinin clearance > 50 mL/min
排除标准
- •Diagnosis and treatment for any other cancer within five years before inclusion or any diagnosis for any cancer. Patients with a skin cancer (except melanoma or carcinoma in situ) are not excluded in case of complete resection.
- •Central nervous system disease
- •Infection requiring an intravenous (IV) antibiotherapy or any severe infection within 14 days before inclusion
- •Diagnosis of any of the following diseases : Waldenström disease, POEMS (polyneuropathy, endocrinopathy, organomegaly, monoclonal gammapathy and skin lesions), plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome or myeloproliferative disorder.
- •Uncontrolled cardiopathy including : uncontrolled hypertension, uncontrolled heart arrhythmia, nonsymptomatic congestive cardiac failure, unstable angina or myocardial infarction within 6 months before inclusion
- •Active infection with hepatitis B or C virus ; positive HIV serology
- •Any comorbidity or severe concomitant disease incompatible with the patient inclusion or interfering with the safety assessment of the study treatments.
- •Psychiatric history or any social condition limiting the patient compliance.
- •Documented allergy to any studied treatment or any of their components.
- •Disability to take oral treatments, inability or refusal to adhere to treatment constraints, or any digestive surgery interfering with oral absorption or treatment tolerance.
- •Any experimental treatment within 30 days prior to the administration of the first dose of the studied treatmentParticipation to another clinical trial
- •Prior participation to a clinical trial with elotuzumab, no matter the arm of treatment.
- •Administration of any pharmaceutical speciality acting against myeloma - such as systemic corticosteroids (>10 mg of prednisone equivalent a day) or clarithromycin - within the month prior to the inclusion. In case of emergency, patients can receive dexamethasone (40mg/day, 4 consecutive days, maximum dose of 160mg) between screening and randomization
研究组 & 干预措施
Elotuzumab
This is a single arm phase II trial to assess the Very Good Partial Response rate of a strategy involving autologous hematopoietic stem cell transplantation, after intensive treatment and followed by consolidation phase, with elotuzumab, dexamethasone, velcade, and thalidomide in elderly patients.
干预措施: Elotuzumab (Drug)
结局指标
主要结局
Maximal response rate Assesment of the International Myeloma Working Group uniform response criteria
时间窗: 1 month after the last consolidation cure
Assesment of the International Myeloma Working Group uniform response criteria
次要结局
- survival and progression-free survival(one year after the last consolidation cure)
- evaluation of the answer to the treatment to improve or maintain the response(12 month of treatment from inclusion)
- Role of the consolidation phase in the improvement or maintenance of the response to the treatment Time before progression(From inclusion to month 36)
- Conversion from negative residual disease to positive residual disease or maintenance of a negative residual disease during all therapeutical phases(from inclusion to month 36)
- correlation between residual disease and duration of the response to the treatment(From inclusion to the end of the 12 treatment-month)
- Tolerance to each phase of treatment (the induction phase, the intensive treatment, the consolidation phase)(From inclusion to month 36)