Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in NDMM

NCT04653246 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20-207
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This research is testing whether the investigational drug isatuximab is safe and effective when used in combination with standard agents for the treatment of newly diagnosed multiple myeloma.

Conditions

Multiple Myeloma; Newly Diagnosed Multiple Myeloma (NDMM); Autologous Stem Cell Transplant

Keywords

Multiple Myeloma; Newly diagnosed multiple myeloma (NDMM); Autologous stem cell transplant (ASCT).; High dose therapy (HDT)

Outcome Measures

Primary Outcomes (1)

• Very Good Partial Response (VGPR)

  proportion of patients who have achieved VGPR or better, according to International Myeloma Working Group (IMWG) criteria (Kumar 2016), by the end of two cycles of induction treatment

  84 days

Secondary Outcomes (6)

• Time to Progression

  time from registration to progression, censored at date last known to be progression-free for those who have not progressed and censored at time of death up to 42 months

• Progression Free Survival

  time from registration to disease progression or death from any cause, censored at date last known to be progression-free for those who have not progressed or died up to 42 months

• Duration of Response

  Time from first response after treatment to the date of disease progression or death from any cause, or date last known progression-free and alive for those who have not progressed or died up to 42 months

• Overall Survival

  Overall survival: time from registration to death from any cause or date last known alive for those who have not died up to 42 months

• Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0

  Induction to up to 3.5 years

Study Arms (1)

Isa-RVD

EXPERIMENTAL

The main study consists of 4 phases a) 28-day screening phase; b) an induction phase inclusive of two 42-day induction treatment cycles: Isatuximab (IV), Bortezomib (SQ). Lenalidomide (PO), Dexamethasone; c) Followed by stem cell mobilization (at the discretion of the Principal Investigator \[PI\]);d) Participants will proceed with either autologous stem cell transplant or two additional induction cycles. \- Induction will be followed by a maintenance phase that continues until disease progression.

Drug: Isatuximab; Drug: Lenalidomide; Drug: Bortezomib Injection; Drug: Dexamethasone

Interventions

Isatuximab DRUG

Via IV at predetermined dosage and predetermined days during each cycle

Also known as: Sarclisa

Isa-RVD

Lenalidomide DRUG

Oral, predetermined dosage and predetermined days during each cycle

Also known as: Revlimid

Isa-RVD

Bortezomib Injection DRUG

SQ Oral, predetermined dosage and predetermined days during each cycle

Isa-RVD

Dexamethasone DRUG

IV or Oral predetermined dosage and predetermined days during each cycle

Isa-RVD

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.
• Provided voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
• Age ≤ 75 years, with patients over the age of 70 requiring PI approval
• Measurable disease defined as at least one of the following:
• Serum M protein ≥ 0.5 g/dL (≥5 g/L)
• Urine M protein ≥ 200 mg/24 hours
• Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65)
• Screening Laboratory evaluations within the following parameters
• Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used within 14 days before first drug administration)
• Platelet count ≥ 75,000 cells/dL (75 x 109/L) if \< 50% BM nucleated cells are plasma cells, ≥ 30,000 cells/dL if ≥ 50% of BM nucleated cells are plasma cells. (without transfusions required during the 3 days prior to the screening hematologic test)
• Total Bilirubin ≤ 2.0 X upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
• Calculated creatinine clearance ≥ 30 mL/min
• Hemoglobin ≤ 8 g/dL
• ECOG performance status ≤ 2 (Appendix A)

You may not qualify if:

• Prior therapy for multiple myeloma
• Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy.
• Central nervous system involvement.
• Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination during the screening period.
• Any medical or psychiatric illness that in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.
• Concurrent uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within the past 6 months.
• Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
• Daily requirement for corticosteroids (equivalent to \> 10 mg/day prednisone for more than 7 days (except for inhalation corticosteroids).
• Concurrent symptomatic amyloidosis or plasma cell leukemia
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
• Known active infection requiring parenteral or oral anti-infective treatment within 14 days of start of therapy.
• Active hepatitis B or hepatitis C viral infection
• Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. Females of childbearing potential (FCBP) unwilling to prevent pregnancy by the use of 2 reliable methods of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to 3 months following the last dose of study treatment and/or who are unwilling or unable to be tested for pregnancy before study treatment initiation (2 negative tests), weekly during 1st month of treatment and then prior each treatment cycle administration or every 2 weeks in case or irregular menstrual cycles up to 3 months following the last dose of study treatment.
• Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions and at least 3 months following study treatment discontinuation, even if has undergone a successful vasectomy.
• Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).

Sponsors & Collaborators

• Jacob Laubach, MD: lead
• Sanofi: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; Lenalidomide; Bortezomib; Dexamethasone

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

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Jacob C Laubach, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 27, 2020
• First Posted: December 4, 2020
• Study Start: July 13, 2021
• Primary Completion: December 15, 2025
• Study Completion (Estimated): January 13, 2029
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)