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Eligibility
for people ages 18 years and up
Location
at San Francisco, California and other locations
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

Primary Objective: Phase 1: To determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) of SAR650984 (Isatuximab). Phase 2 (stage 1): To evaluate the activity of single-agent Isatuximab at different doses/schedules and to select dose and regimen to further evaluate the overall response rate (ORR) of Isatuximab as single agent or in combination with dexamethasone. Phase 2 (stage 2): To evaluate the activity in terms of overall response rate (ORR) of Isatuximab at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm). Secondary Objectives: Phase 1: - To characterize the global safety profile including cumulative toxicities. - To evaluate the pharmacokinetic (PK) profile of Isatuximab in the proposed dosing schedule(s). - To assess the pharmacodynamics (PD), immune response, and preliminary disease response. Phase 2 (stage 1): to evaluate the following objectives for Isatuximab as single agent: - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival. Phase 2 (stage 2): to evaluate the following objectives in each arm (ISA and ISAdex): - Safety - Efficacy as measured by duration of response, clinical benefit rate, progression free survival, overall survival.

Official Title

A Phase I/2 Dose Escalation Safety, Pharmacokinetic and Efficacy Study of Multiple Intravenous Administrations of a Humanized Monoclonal Antibody (SAR650984) Against CD38 in Patients With Selected CD38+ Hematological Malignancies

Details

The Phase 1 study duration for an individual patient will include a screening period for inclusion of up to 2 weeks, treatment with Isatuximab QW (every week) or Q2W (every 2 weeks) unless discontinued earlier due to safety or disease progression. Patients will be followed for a minimum of 30 days following the last use of study drug or more than 30 days in case of unresolved toxicity, or up to initiation of another anticancer treatment.

The Phase 2 study duration for an individual patient will include a screening period for inclusion of up to 3 weeks, then a treatment period and a follow up period. Treatment will continue until disease progression, unacceptable adverse reactions or other reasons for discontinuation. Patients will be followed every 3 months following the last use of study drug until death or study cutoff whichever comes first.

Keywords

Hematological Malignancy Dexamethasone acetate Dexamethasone Dexamethasone 21-phosphate Daratumumab BB 1101 Antibodies, Monoclonal Antibodies

Eligibility

You can join if…

Open to people ages 18 years and up

Phase 1:

  • For dose escalation cohorts, patients with confirmed selected CD38+ hematological malignancies as specified below who have progressed on after standard therapy or for whom there is no effective standard therapy (refractory/relapsed patients). B-cell Non-Hodgkin-lymphoma/leukemia (NHL) patients having at least 1 measurable lesion. Multiple myeloma (MM) patients with measurable M-protein serum and/or 24-hour urine. Acute myeloid leukemia (AML) patients, all types except M3 based on French-American-British (FAB) classification. Acute Lymphoblastic Leukemia (B-cell ALL) patients. Chronic lymphocytic leukemia (CLL) patients.
  • For expansion cohorts, patients with relapsed/refractory MM with measurable M-protein(serum M-protein of>0.5 g/dL and/or urine M-protein of>200 mg (24-hr urine)) or elevated serum free light chains (FLC)>10 mg/dL with abnormal FLC ratio) who have progressed on or after standard therapy that includes an iMiD and a proteasome inhibitor and who meet the protocol defined criteria for standard risk or high risk.

Phase 2:

  • Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, and have evidence of disease progression based on International Myeloma

Working Group (IMWG) criteria: Serum M-protein ≥1 g/dL, or urine M-protein ≥200 mg/24 hours or in the absence of measurable m-protein, serum FLC ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda FLC ratio (<0.26 or>1.65).

  • Patients must have received at least three prior lines of therapy for MM and must include treatment with an Immunomodulatory drug (IMiD) (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (PI) (for ≥2 cycles or ≥2 months of treatment)OR patients whose disease is double refractory to an IMiD and a PI. For patients who have received more than 1 type of IMiD and PI, their disease must be refractory to the most recent one.
  • Patients must have achieved a minimal response or better to at least one prior line of therapy.
  • Patients must have received an alkylating agent (≥2 cycles or ≥2 months) either alone or in combination with other MM treatments.
  • Stage 2 only: Patients must have evidence of disease progression on or after the most recent prior regimen based on IMWG criteria.

You CAN'T join if...

Phase 1:

  • Karnofsky performance status <60
  • Poor bone marrow reserve
  • Poor organ function
  • Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that is not amenable to pre-medication with steroids and H2 blockers
  • Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results
  • Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results

Phase 2:

  • Patients with multiple myeloma immunoglobulin M (IgM) subtype
  • Previous treatment with any anti-CD38 therapy
  • Patients with concurrent plasma cell leukemia
  • Patients with known or suspected amyloidosis
  • Karnofsky performance status <60 (stage 1)/ECOG Performance status>2 (stage 2).
  • Poor bone marrow reserve
  • Poor organ function
  • Known intolerance to infused protein products, sucrose, histidine, polysorbate 80 or known hypersensitivity to any of the components of the study therapy that is not amenable to pre-medication with steroids and H2 blockers
  • Any serious active disease (including clinically significant infection that is chronic, recurrent, or active) or co-morbid condition, which, in the opinion of the investigator, could interfere with the safety, the compliance with the study or with the interpretation of the results
  • Any severe underlying medical conditions including presence of laboratory abnormalities, which could impair the ability to participate in the study or the interpretation of its results

    The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Locations

  • Investigational Site Number 840005 accepting new patients
    San Francisco, California, 94117, United States
  • Investigational Site Number 840003 accepting new patients
    Scottsdale, Arizona, 85054, United States
  • Investigational Site Number 840002 accepting new patients
    Salt Lake City, Utah, 84112-5550, United States
  • Investigational Site Number 840012 accepting new patients
    Seattle, Washington, 98109, United States
  • Investigational Site Number 840018 accepting new patients
    Rochester, Minnesota, 55905, United States
  • Investigational Site Number 840013 accepting new patients
    Saint Louis, Missouri, 63110, United States
  • Investigational Site Number 840017 accepting new patients
    Milwaukee, Wisconsin, 53226, United States
  • Investigational Site Number 840010 accepting new patients
    Chicago, Illinois, 60637, United States
  • Investigational Site Number 840001 accepting new patients
    Nashville, Tennessee, 37232, United States
  • Investigational Site Number 840004 completed
    Cincinnati, Ohio, 45267-0542, United States
  • Investigational Site Number 840022 accepting new patients
    Ann Arbor, Michigan, 48109-0759, United States
  • Investigational Site Number 840027 accepting new patients
    Detroit, Michigan, 48201, United States
  • Investigational Site Number 840009 accepting new patients
    Atlanta, Georgia, 30322, United States
  • Investigational Site Number 840024 accepting new patients
    Cleveland, Ohio, 44195, United States
  • Investigational Site Number 840016 accepting new patients
    Durham, North Carolina, 27707, United States
  • Investigational Site Number 840011 accepting new patients
    Hackensack, New Jersey, 07601, United States
  • Investigational Site Number 840014 completed
    New York, New York, 10021, United States
  • Investigational Site Number 604001 accepting new patients
    Arequipa, Peru
  • Investigational Site Number 643003 accepting new patients
    Novosibirsk, 630087, Russian Federation
  • Investigational Site Number 643001 accepting new patients
    Petrozavodsk, 185019, Russian Federation
  • Investigational Site Number 643004 accepting new patients
    St-Petersburg, 194291, Russian Federation
  • Investigational Site Number 246001 accepting new patients
    Helsinki, 00029, Finland
  • Investigational Site Number 246002 accepting new patients
    Turku, 20521, Finland
  • Investigational Site Number 056001 accepting new patients
    Antwerpen, 2060, Belgium
  • Investigational Site Number 250003 completed
    Nantes Cedex 01, 44093, France
  • Investigational Site Number 250004 completed
    Pierre Benite, 69310, France
  • Investigational Site Number 250001 completed
    Toulouse Cedex 9, 31059, France
  • Investigational Site Number 152001 accepting new patients
    Temuco, 4810469, Chile
  • Investigational Site Number 724002 accepting new patients
    Pamplona, 31008, Spain
  • Investigational Site Number 724001 accepting new patients
    Salamanca, 37007, Spain
  • Investigational Site Number 380001 accepting new patients
    Bologna, 40138, Italy
  • Investigational Site Number 804001 accepting new patients
    Kiev, 04112, Ukraine
  • Investigational Site Number 804004 accepting new patients
    Vinnytsya, 21018, Ukraine
  • Investigational Site Number 300001 accepting new patients
    Athens, 11528, Greece
  • Investigational Site Number 792002 accepting new patients
    Ankara, 06200, Turkey
  • Investigational Site Number 792001 accepting new patients
    İstanbul, Turkey
  • Investigational Site Number 792004 accepting new patients
    Samsun, 55139, Turkey

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Sanofi
ID
NCT01084252
Phase
Phase 1/2
Lead Scientist
Thomas Martin
Study Type
Interventional
Last Updated
May 1, 2017
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