Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04965155
Other study ID # ISABEL
Secondary ID
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date March 21, 2021
Est. completion date March 31, 2027

Study information

Verified date December 2023
Source EMN Research Italy
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an open label phase II study designed to assess the efficacy and safety of the combination isatuximab-dexamethasone pre and post transplant in relapsed MM patients. Before enrolment, patients have already received a reinduction therapy, as per local protocols, in order to achieve an optimal cytoreduction. Since carfilzomib-based regimens (eg. carfilzomib-lenalidomide-dexamethasone or carfilzomib-dexamethasone) are the current standard in Italy, for uniformity the use of one of these combinations is recommended. However, any cytoreductive treatment, excluding anti-CD38 antibodies containing regimens, as per local practice, is acceptable. During this period, if necessary, it will be possible to mobilize and collect peripheral blood stem cells. After the pre-enrollment cytoreduction period (reinduction therapy), patients have achieved at least a PR according to IMWG Response criteria. After study enrolment, patients will receive 3 courses of isatuximab in combination with dexamethasone; after cycle 3 patients will receive ASCT, that will be conditioned with melphalan and will be followed by reinfusion of cryopreserved autologous stem cells. At 2 months after ASCT, patients will start maintenance, consisting in the administration of isatuximab in combination with dexamethasone for 12 cycles. Starting from cycle 13 onwards, only isatuximab will be administered until progression or intolerance.


Read more »

Study Design


Intervention

Drug:
Isatuximab-dexamethasone
Isatuximab 10 mg/kg IV: 1,8,15 and 22 at cycle 1; days 1 and 15 at cycles 2-3 Dexamethasone 40 mg OS: 1,8,15 and 22 at cycle 1; days 1 and 15 at cycles 2-3

See more »

Sponsors (1)

Lead Sponsor Collaborator
EMN Research Italy

Country where clinical trial is conducted

Italy, 

Outcome

Type Measure Description Time frame Safety issue
Primary MRD negativity 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. Within 12 months after ASCT
Secondary Response rate Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after induction, transplant and maintenance. 5/6 years
Secondary TTP (time to progression) 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. 5/6 years
Secondary PFS (progression free survival) 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. 5/6 years
Secondary TNT (time to next therapy) 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. 5/6 years
Secondary PFS2 (progression free survival 2) PFS2 will be measured from the date of ICF to the date of observation of second disease progression (i.e. progression after the second line of therapy) 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, have not progressed, and are still alive will also be censored at the time of last contact. 5/6 years
Secondary OS (overall survival) 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 Page 48 of 72 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. 5/6 years
Secondary DOR (duration of response) 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. 5/6 years
Secondary Time to PR (time to partial response) Time to PR will be measured from the date of ICF to the date of first observation of PR (Partial Response). 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. 5/6 years
Secondary Time to VGPR (time to very good partial response) 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 censored at the time of last contact. 5/6 years
Secondary Time to CR (time to complete response) Time to CR will be measured from the date of ICF to the date of first observation of CR (Complete Partial Response). 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 time of last contact. Difference will be calculated in 30-day months. 5/6 years
Secondary Time to sCR (time to stringent complete response) 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. 5/6 years
Secondary Rate of 1 year sustained MRD (minimal residue disease) negativity Rate of 1 year sustained MRD negativity by NGF will be also evaluated, and correlated with PFS and OS. 5/6 years
Secondary MRD (minimal residue disease) negativity 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. 5/6 years
Secondary 24 months MRD negativity rate 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. 5/6 years
Secondary Analysis of safety 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. 5/6 years
Secondary Dose reduction rate Dose reduction will be done primarily by tabulation of the incidence of dose reduction and causes. 5/6 years
Secondary Time to discontinuation of study drug 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. 5/6 years
Secondary Relative dose estimations for each study drugs Relative dose will be evaluated consider the ration between the administered and the planned dose. Relative dose will be estimated for each study drugs. 5/6 years
See also
  Status Clinical Trial Phase
Active, not recruiting NCT04083534 - First In Human (FIH) Study of REGN5459 in Adult Patients With Relapsed or Refractory Multiple Myeloma (MM) Phase 1/Phase 2
Recruiting NCT06119685 - IDP-023 as a Single Agent and in Combination With Antibody Therapies in Patients With Advanced Hematologic Cancers Phase 1/Phase 2
Active, not recruiting NCT05577000 - Anti-BCMA Chimeric Antigen Receptor T Cells for Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT01118689 - Dose Escalation Study of MLN0128 in Relapsed or Refractory Multiple Myeloma or Waldenstrom Macroglobulinemia Phase 1
Withdrawn NCT04802031 - Rapid-infusion Isatuximab in Relapsed/Refractory Multiple Myeloma Phase 2
Completed NCT02401295 - ATRA, Celecoxib, and Itraconazole as Maintenance Phase 1
Active, not recruiting NCT00603447 - Phase 1b Multicenter Study of Carfilzomib With Lenalidomide and Dexamethasone in Relapsed Multiple Myeloma Phase 1
Active, not recruiting NCT02722668 - UCB Transplant for Hematological Diseases Using a Non Myeloablative Prep Phase 2
Completed NCT00592579 - A Phase 2 Study With Panzem in Patients With Relapsed or Plateau Phase Multiple Myeloma Phase 2
Not yet recruiting NCT06433947 - Study to Assess Safety and Tolerability of OPN-6602 in Subjects With Relapsed and/or Refractory Multiple Myeloma Phase 1
Recruiting NCT06304636 - Descartes-15 for Patients With Relapsed/Refractory Multiple Myeloma Phase 1
Completed NCT03158688 - Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. Phase 3
Completed NCT04434469 - A Study Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma Phase 1
Completed NCT01080391 - Study Comparing Carfilzomib, Lenalidomide, and Dexamethasone (CRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed Multiple Myeloma Phase 3
Not yet recruiting NCT06348108 - Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT01949532 - Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Multiple Myeloma and Renal Disease Phase 1
Active, not recruiting NCT04398485 - A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma Phase 1
Recruiting NCT03091933 - Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion) Phase 1/Phase 2
Completed NCT01272466 - Vaccination With Peptides From Anti-apoptotic Proteins in Relapsed Multiple Myeloma Phase 1/Phase 2
Recruiting NCT05896228 - Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma Phase 2