A Trial for Relapsed Multiple Myeloma Patients (Isatuximab-dexamethasone)

NCT04965155 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ISABEL
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Relapsed Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Response rate

  5/6 years

• TTP (time to progression)

  5/6 years

• PFS (progression free survival)

  5/6 years

• TNT (time to next therapy)

  5/6 years

• PFS2 (progression free survival 2)

  5/6 years

Study Arms (1)

Isatuximab-Dexamethasone

EXPERIMENTAL

Isatuximab-Dexamethasone pre and post transplant in relapsed multiple myeloma patients.

Drug: Isatuximab-dexamethasone

Interventions

Isatuximab-dexamethasone DRUG

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

Isatuximab-Dexamethasone

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has given voluntary written informed consent
• 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-lenalidomidedexamethasone 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 documented relapsed MM as per IMWG criteria, and achieved at least a partial remission with treatments as per local guidelines
• Subject must have at least 2.0 x 106 CD34+/Kg cryopreserved autologous stem cells
• Subject must have an ECOG Performance Status score of 0, 1
• Subject must have the following laboratory values:
• Platelet count =50 x 109/L (=30 x 109 /L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to drug administration)
• Absolute neutrophil count (ANC) = 1 x 109/L without the use of growth factors
• Corrected serum calcium =14 mg/dL (3.5 mmol/L)
• Alanine transaminase (ALT): = 3 x the ULN
• Total bilirubin: = 2 x the ULN

You may not qualify if:

• Previous therapy with daratumumab, isatuximab or any other anti-CD38 monoclonal antibody
• MM localization to the central nervous system
• Subjects who have received any investigational drug within 14 days or 5 half-lives of the investigational drug from eligibility confirmation, whichever is longer
• 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
• 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 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 H2 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:
• LVEF \<50%
• Myocardial infarction within 6 months before eligibility confirmation, or unstable or
• Uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV)
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5 Grade 2 or higher) or clinically significant ECG abnormalities

Sponsors & Collaborators

• EMN Trial Office S.r.l. Impresa Sociale: lead

Study Sites (14)

AOU Ospedali Riuniti Umberto I

Ancona, Italy

Location

AOU Policlinico di Bari

Bari, Italy

Location

AOU di Bologna

Bologna, Italy

Location

Ospedale di Bolzano - Azienda Sanitaria dell'Alto Adige

Bolzano, Italy

Location

AOU Policlinico S. Martino

Genova, Italy

Location

I.R.C.C.S. Ospedale S. Raffaele

Milan, Italy

Location

AOU Federico II

Napoli, Italy

Location

AO di Padova

Padua, Italy

Location

AO di Perugia-Ospedale S. Maria della Misericordia

Perugia, Italy

Location

Policlinico Umberto I - Università 'Sapienza'

Roma, Italy

Location

AO S. Maria

Terni, Italy

Location

AOU Città della Salute e della Scienza di Torino

Torino, Italy

Location

AOU Ospedali Riuniti di Trieste

Trieste, Italy

Location

Ospedale S. Maria della Misericordia di Udine

Udine, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Isatuximab-dexamethasone pre and post transplant

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 16, 2021
• Study Start: March 21, 2021
• Primary Completion: November 28, 2023
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 25, 2025

Record last verified: 2025-02

Locations

IT (14)