Clinical Trials /

Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

NCT04653246

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
  • Official Title: Phase 2, Multi-Center, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 20-207
  • NCT ID: NCT04653246

Conditions

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

Interventions

DrugSynonymsArms
IsatuximabSarclisaIsa-RVD
LenalidomideRevlimidIsa-RVD
Bortezomib InjectionIsa-RVD
DexamethasoneIsa-RVD

Purpose

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.

Detailed Description

      This is a multi-center, single-arm, open-label, Phase 2 study in patients with newly
      diagnosed multiple myeloma (NDMM) eligible for high dose therapy (HDT) and autologous stem
      cell transplant (ASCT).

      In this research study, investigators are evaluating whether isatuximab is safe and effective
      in participants with newly diagnosed multiple myeloma when given in combination with
      lenalidomide, bortezomib, and dexamethsone.

        -  This research study involves administration of a four-drug chemotherapy regimen that
           combines the Investigational drug isatuximab with a standard chemotherapy regimen
           comprised of lenalidomide, bortezomib, and dexamethasone.

        -  This 4-drug regimen is not considered standard of the treatment of newly diagnosed
           multiple myeloma.

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug or combination of drugs to learn whether the
      drug works in treating a specific disease. "Investigational" means that the drug is being
      studied.

      The U.S. Food and Drug Administration (FDA) has approved lenalidomide, bortezomib, and
      dexamethasone as treatment options for this disease but the combination of these agents with
      isatuximab hasn't been approved.
    

Trial Arms

NameTypeDescriptionInterventions
Isa-RVDExperimentalThe 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.
  • Isatuximab
  • Lenalidomide
  • Bortezomib Injection
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  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)

          -  Participant agrees to be registered into the mandatory Revassist REMS® program, and be
             willing and able to comply with the requirements of the RevAssist REMS® program.

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Participant is considered eligible for ASCT by the treating physician.

        Exclusion Criteria:

          -  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).

               -  Note 2: True abstinence is acceptable when this is in line with the preferred and
                  usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation,
                  symptothermal, post-ovulation methods) and withdrawal are not acceptable methods
                  of contraception.

          -  Receiving any other investigational agents

          -  Inability to tolerate thromboprophylaxis

          -  Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base
             and hydrochloride salt), boron, mannitol, and polysorbate 80, or to any of the
             components of the study therapy

          -  Hypersensitivity to steroids or H2 blockers that would prohibit further treatment with
             these agents.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:75 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:stringent Complete Response (sCR)
Time Frame:84 days
Safety Issue:
Description:proportion of patients who have achieved sCR, according to IMWG criteria, by the end of two cycles of induction treatment. Response will be evaluated using a Simon optimal two-stage design.

Secondary Outcome Measures

Measure:Time to Progression
Time Frame: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
Safety Issue:
Description:Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs). Time to progression is defined as 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 for those who died.
Measure:Progression Free Survival
Time Frame: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
Safety Issue:
Description:- Progression-free survival (PFS) will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median Time to progression (TTP) with 95% confidence intervals (CIs 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
Measure:Duration of Response
Time Frame: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
Safety Issue:
Description:Duration of Response will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs 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.
Measure:Overall Survival
Time Frame: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
Safety Issue:
Description:Overall Survival will be analyzed similarly to time to progression: Progression-free probabilities over time will be estimated using the Kaplan-Meier method (Kaplan, 1958), presenting an estimate of median time to progression (TTP) with 95% confidence intervals (CIs Overall survival: time from registration to death from any cause or date last known alive for those who have not died
Measure:Number of Participants with Treatment Related Adverse Events as Assessed by CTCAE v 5.0
Time Frame:Induction to up to 3.5 years
Safety Issue:
Description:Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) v5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Jacob Laubach

Trial Keywords

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

Last Updated

December 4, 2020