SAR650984 (Isatuximab), Lenalidomide, and Dexamethasone in Combination in RRMM Patients

NCT01749969 | Completed Phase 1

• 2 other identifiers: TCD11863U1111-1119-3107
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 5

Brief Summary

Primary Objectives:

• To determine the maximum tolerated dose of SAR650984 (isatuximab) with lenalidomide and dexamethasone (LD) in patients with relapsed or refractory multiple myeloma.
• Expansion Phase Only: To further evaluate preliminary evidence of antitumor activity (objective response rate \[ORR\]) of SAR650984 (isatuximab) in combination with LD using International Myeloma Working Group (IMWG) criteria. Secondary Objectives:
• To evaluate the safety, including immunogenicity, of SAR650984 (isatuximab) in combination with LD in relapsed or refractory multiple myeloma. The severity, frequency and incidence of all toxicities will be assessed.
• To evaluate the pharmacokinetics (PK) of SAR650984 (isatuximab) when administered in combination with LD and the PK of lenalidomide in combination with SAR650984 and dexamethasone.
• To assess the relationship between clinical (adverse event \[AE\] and/or tumor response) effects and pharmacologic parameters (PK/pharmacodynamics), and/or biologic (correlative laboratory) results.
• For the dose expansion phase, estimate the activity (ORR) using IMWG defined response criteria of SAR650984 (isatuximab) plus LD.
• To describe progression-free survival (PFS) in patients treated with this combination.

Conditions

Plasma Cell Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events when treated with SAR650984 (isatuximab) in combination with LD

  Up to 30 days for patients experiencing progressive disease and continuously while patients are on treatment

Secondary Outcomes (10)

• Preliminary assessment of overall response rate

  9 months from the last investigational medicinal product (IMP)/non-IMP (NIMP) administration

• Preliminary assessment of progression-free survival (PFS)

  Up to disease progression

• Assessment of PK parameters - maximum concentration (Cmax)

  Up to disease progression plus 60 days

• Assessment of PK parameters - time to reach Cmax (Tmax)

  Up to disease progression plus 60 days

• Assessment of PK parameters - concentration observed at end of infusion (Ceoi)

  Up to disease progression plus 60 days

Study Arms (1)

SAR650984 (isatuximab)

EXPERIMENTAL

SAR650984 (isatuximab) (escalating dose) plus lenalidomide 25 mg on Days 1 to 21 plus dexamethasone 40 mg on Days 1, 8, 15, 22 in 28-day cycles for all cohorts up to disease progression. For Q2W cohorts: SAR650984 (isatuximab) on Days 1 and 15 of every cycle. For QW/Q2W cohorts: SAR650984 (isatuximab) on Days 1, 8, 15, and 22 of first cycle and Days 1 and 15 of every subsequent cycle.

Drug: isatuximab SAR650984; Drug: lenalidomide; Drug: dexamethasone

Interventions

isatuximab SAR650984 DRUG

Pharmaceutical form:solution Route of administration: intravenous

Also known as: Sarclisa

SAR650984 (isatuximab)

lenalidomide DRUG

Pharmaceutical form:capsules Route of administration: oral

Also known as: Revlimid

SAR650984 (isatuximab)

dexamethasone DRUG

Pharmaceutical form:solution or tablet Route of administration: intravenous or oral

SAR650984 (isatuximab)

Eligibility Criteria

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

You may qualify if:

• Male or female patients age 18 years or older. Diagnosis of multiple myeloma and documentation of at least 2 prior therapies (induction therapy, autologous stem cell transplant, consolidation and maintenance therapy is considered one prior therapy); there is no maximum number of prior regimens and prior bone marrow transplant is acceptable.
• Confirmed evidence of disease progression from immediately prior MM therapy or refractory to the immediately prior therapy.
• Patients may have received prior immunomodulatory drugs (IMiDs®) (eg, lenalidomide or thalidomide).
• Patients with measurable disease. Patients with a Karnofsky ≥60% performance status. Females of childbearing potential (FCBP). Voluntary written informed consent before performance of any study-related procedure not part of routine medical care with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).
• Able to take aspirin daily as prophylactic anti-coagulation therapy (patients intolerant to aspirin may use warfarin, low molecular weight heparin or equivalent anti-platelet therapy).
• Adequate organ function.

You may not qualify if:

• 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.
• Prior anti-cancer therapy (chemotherapy, targeted agents, radiotherapy, and immunotherapy) within 21 days except for alkylating agents (eg, melphalan) where 28 days will be required or participated in another clinical trial during the past 30 days.
• History of significant cardiovascular disease within the past 6 months, unless the disease is well-controlled.
• Prior autologous stem cell transplant within 12 weeks of the first dose of study treatment and/or prior allogeneic transplant within 1 year or has evidence of active graft-versus-host disease (GVHD) requiring \>10 mg prednisone daily.
• Daily requirement for corticosteroids (\>10 mg prednisone qd for 7 consecutive days) (except for inhalation corticosteroids and patients being treated for adrenal insufficiency/replacement therapy).
• Evidence of mucosal or internal bleeding. Prior radiation therapy or major surgical procedure within 4 weeks of the first dose of study treatment.
• Known active infection requiring parenteral or oral anti-infective treatment. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation.
• Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient.
• Hypersensitivity to any of the components of study therapy that is not amenable to premedication with steroids and H2 blockers.
• Known human immunodeficiency virus (HIV) or active hepatitis B or C viral infection.
• Neuropathy ≥ Grade 3 or painful neuropathy ≥ Grade 2. Gastro-intestinal abnormalities, including bowel obstruction, inability to take oral medication, requirement for intravenous (IV) alimentation, active peptic ulcer or prior surgical procedures or bowel resection affecting absorption.
• Pregnancy.
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (5)

Investigational Site Number 840004

San Francisco, California, 94117, United States

Location

Investigational Site Number 840001

Tampa, Florida, 33612, United States

Location

Investigational Site Number 840002

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840005

New York, New York, 10021, United States

Location

Investigational Site Number 840003

Columbus, Ohio, 43210, United States

Location

Related Publications (2)

• Sun H, Martin TG, Marra J, Kong D, Keats J, Mace S, Chiron M, Wolf JL, Venstrom JM, Rajalingam R. Individualized genetic makeup that controls natural killer cell function influences the efficacy of isatuximab immunotherapy in patients with multiple myeloma. J Immunother Cancer. 2021 Jul;9(7):e002958. doi: 10.1136/jitc-2021-002958.

  PMID: 34272304 DERIVED

• Martin T, Baz R, Benson DM, Lendvai N, Wolf J, Munster P, Lesokhin AM, Wack C, Charpentier E, Campana F, Vij R. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017 Jun 22;129(25):3294-3303. doi: 10.1182/blood-2016-09-740787. Epub 2017 May 8.

  PMID: 28483761 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; Lenalidomide; 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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2012
• First Posted: December 17, 2012
• Study Start: February 6, 2013
• Primary Completion: June 20, 2023
• Study Completion: June 20, 2023
• Last Updated: July 13, 2023

Record last verified: 2023-07

Locations

US (5)