2024-513397-21-00招募中2 期
Isatuximab and Autologous Hematopoietic Stem Cell Transplantation for Relapsed Multiple Myeloma Patients (Isabel study)
Emn Trial Office S.r.l. Impresa Sociale7 个研究点 分布在 1 个国家目标入组 25 人开始时间: 2024年7月31日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 25
- 试验地点
- 7
- 主要终点
- The rate of MRD negativity is determined as the proportion of patients with NGF MRD negativity (10-5 sensitivity level) within 12 months after ASCT using the intention-to-treat principle. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.
研究概览
简要总结
The primary objective of the study is the evaluation of isatuximab and salvage ASCT efficacy.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Maintenance
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Patient has given voluntary written informed consent
- •1.1 Platelet count ≥50 x 10^9/L (≥30 x 10^9 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration)
- •1.2 Absolute neutrophil count (ANC) ≥ 1 x 10^9/L without the use of growth factors
- •1.3 Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)
- •1.4 Alanine transaminase (ALT): ≤ 3 x the ULN
- •1.5 Total bilirubin: ≤ 2 x the ULN
- •1.6 Calculated or measured creatinine clearance: ≥ 30 mL/minute
- •Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies:
- •2.1 They are not females of childbearing potential (FCBP)
- •2.2 They are FCBP who have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours of starting study medication and before each cycle of study treatment and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control during the intervention period and for at least 5 months after the last dose of study treatment. Of note: contraception duration should take also into consideration any backbone therapy
- •Male subjects must agree to use contraception on this protocol during the intervention period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period
- •Patient is willing and able to comply with the study visits and procedures required per protocol
- •Subject must have at least 18 and ≤ 70 years of age
- •Patient has a life-expectancy ≥ 3 months
- •Subject has received an ASCT in the first line of therapy with a progression/relapse after at least 24 months
- •Subject must have received any cytoreductive treatment, excluding anti-CD38 antibodies containing regimens, as per local practice for the first relapse, according to local guidelines. Carfilzomib-based combinations are recommended (eg. carfilzomib-lenalidomide-dexamethasone or carfilzomib-dexamethasone). After the salvage duration phase (reinduction therapy), subject has achieved at least a PR according to IMWG Response criteria.
- •Subject must have at least 2.0 x 10^6 CD34+/Kg cryopreserved autologous stem cells
- •Subject must have an ECOG Performance Status score of 0, 1
- •1.Subject must have the following laboratory values:
排除标准
- •Previous therapy with daratumumab, isatuximab or any other anti-CD38 monoclonal antibody
- •Active HCV infection: positive HCV RNA and negative anti-HCV. Of note:
- •2.1 Subjects with antiviral therapy for HCV started before initiation of study treatment and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
- •2.2 Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible.
- •Subject with any concurrent, clinically significant, uncontrolled medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
- •Subject with active tuberculosis and systemic or severe infections requiring treatment with an antibiotic parenteral administration
- •Subject with hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H1 blockers or would prohibit further treatment with these agents
- •Subject with pulmonary deficit, defined as FEV1 <65% and/or DLCO <65%
- •Subject with clinically significant cardiac disease, including:
- •3.1 LVEF <50%
- •3.2 Myocardial infarction within 6 months before eligibility confirmation, or unstable
- •MM localization to the central nervous system
- •3.3 Uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV)
- •3.4 Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Version 5 Grade 2 or higher) or clinically significant ECG abnormalities
- •3.5 Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec
- •Subjects who have received any investigational drug within 14 days or 5 half-lives of the investigational drug from eligibility confirmation, whichever is longer. In case of very aggressive disease, delay could be shortened after agreement between Sponsor and Investigator, in absence of residual toxicities from previous therapy
- •Subjects who have received an allogeneic stem cell transplant
- •Subject with a history of malignancy (other than multiple myeloma) within 3 years before the date of eligibility confirmation (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, in agreement with the medical monitor, is considered cured with minimal risk of recurrence within 3 years)
- •Subject is known to be seropositive for human immunodeficiency virus (HIV) or with an active hepatitis A, B and C infection, defined as a positive test for hepatitis B surface antigen [HBsAg] and a positivity for HAV-RNA, HBV-DNA or HCV-RNA.
- •Uncontrolled or active HBV infection: patients with positive HBsAg and/or HBV DNA. Of note:
- •1.1 Subjects can be eligible if: anti-HBc IgG is positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of study treatment, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
- •1.2 Subjects with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.
结局指标
主要结局
The rate of MRD negativity is determined as the proportion of patients with NGF MRD negativity (10-5 sensitivity level) within 12 months after ASCT using the intention-to-treat principle. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.
The rate of MRD negativity is determined as the proportion of patients with NGF MRD negativity (10-5 sensitivity level) within 12 months after ASCT using the intention-to-treat principle. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.
次要结局
- Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after induction, transplant and maintenance.
- TTP will be measured from the date of ICF to the date of first observation of PD, or deaths for PD. Subjects who have not progressed or who withdraw from the study or die from causes other than PD will be censored at the time of the last complete disease assessment. Subjects lost to follow-up will also be censored at the time of last complete disease assessment
- PFS will be measured from the date of ICF to the date of first observation of PD, or death from any cause as an event. Subjects who have not progressed or who withdraw from the study or who were lost to follow-up will be censored at the time of the last complete disease assessment.
- TNT will be measured from the date of eligibility confirmation to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event. Subjects who have not progressed or who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects lost to FU will also be censored at the time of last contact.
- PFS2 will be measured from the date of ICF to the date of observation of second disease progression or death to any cause as an event. In case of date of second progression is not available, date of start of third line treatment can be used. Subjects who have not progressed or who withdraw from the study will be censored at the time of the last complete disease assessment. All subjects who were lost to follow-up prior to the end of the study, h
- OS is defined as the time between ICF date and death, regardless cause of death. Subjects who withdraw consent will be censored at the time of withdrawal. Subjects who are still alive at the cut-off date of final analysis will be censored at the cut-off date. Subjects lost to FU will also be censored at the time of last contact
- DOR is defined as time between first documentation of response (achievement of at least a PR) and PD with deaths owning to causes other than progression not counted, but censored. Responders without disease progression at the cut-off date of final analysis will be censored either at the time of lost to follow-up, at the time of death due to other cause than PD, or at the time of last contact.
- Time to PR will be measured from the date of ICF to the date of first observation of PR Subjects who achieved response better than PR will be consider that PR is achieved. Subjects who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects have not achieved a PR, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censored at the time of last contact.
- Time to VGPR will be measured from the date of ICF to the date of first observation of VGPR (Very Good Partial Response). Subjects who achieved response better than VGPR will be consider that VGPR is achieved. Subjects who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects have not achieved a VGPR, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censor
- Time to CR will be measured from the date of ICF to the date of first observation of CR.Subjects who achieved response better than CR will be consider that CR is achieved. Subjects who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects have not achieved a CR, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censored at the t
- Time to sCR will be measured from the date of ICF to the date of first observation of sCR (stringent Complete Partial Response). Subjects who withdraw from the study will be censored at the time of the last complete disease assessment. Subjects have not achieved a sCR, and are still alive at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censored at the time of last contact. Difference will be calculated in 30-day months.
- Rate of 1 year sustained MRD negativity by NGF will be also evaluated, and correlated with PFS and OS.
- The rate of MRD negativity is determined as the proportion of patients with NGF MRD negativity (10-5 sensitivity level) within 12 months after ASCT using the intention-to-treat principle. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.
- The 24 months MRD negativity rate is determined as the proportion of patients with MRD negativity (≥10-5 sensitivity level, NGF) after 12 months using ITT principle. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment/sample not adequate.
- The analysis of safety as defined by type, frequency and severity will be done primarily by tabulation of the incidence of Adverse Events as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. In the by-subject analysis, a subject having the same event more than once will be counted only once. Adverse Events will be summarized by worst CTCAE grade.
- Dose reduction will be done primarily by tabulation of the incidence of dose reduction and causes.
- Time to discontinuation will be measured from the date of first dose of study drugs to the date of discontinuation due to AE or Death for AE/SPM. Subjects who discontinued drugs due to PD, or death for cause other than AE/SPM will be considered a competitive event. Subjects has not discontinued, and are still alive and on treatment at the cut-off date of final analysis will be censored at the cut-off date. All subjects who were lost to FU will also be censored at the time of last contact.
- Relative dose will be evaluated consider the ration between the administered and the planned dose. Relative dose will be estimated for each study drugs.
研究者
Vittorio Montefusco
Scientific
Emn Trial Office S.r.l. Impresa Sociale
研究点 (7)
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