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Trial record 1 of 1 for:    TED15138
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First in Human Testing of Dose-escalation of SAR440234 in Patients With Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03594955
Recruitment Status : Recruiting
First Posted : July 20, 2018
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

  • Dose escalation: To determine the maximum tolerated dose (MTD) of SAR440234 administered as a single agent in patients with R/R AML (relapsed or refractory acute myeloid leukemia), HR-MDS (high risk myelodysplastic syndrome), or B-ALL (B-cell acute lymphoblastic leukemia), and determine the recommended phase 2 dose (RP2D) for the subsequent Expansion part.
  • Expansion part: To assess the activity of single agent SAR440234 at the RP2D in patients with R/R AML or HR-MDS.

Secondary Objective:

  • To characterize the safety profile including cumulative adverse drug reactions.
  • To evaluate the potential immunogenicity of SAR440234.
  • To assess any preliminary evidence of hematologic response in the Dose Escalation Part.

Condition or disease Intervention/treatment Phase
Leukaemia Drug: SAR440234 Phase 1 Phase 2

Detailed Description:
The duration of the study for the patients will include a period for screening of up to 14 days. The cycle duration is 42 days. Patients will continue study treatment as long as clinical benefit is possible or until disease progression, unacceptable adverse reaction, patient's decision to stop treatment, or other reason of discontinuation. After study treatment discontinuation patients will return to the study site 30 days after the last administration of SAR440234 for end of treatment assessments. Patients without documented disease progression at the end of a treatment visit who have not yet started treatment with another anti-cancer therapy will proceed with monthly follow-up visits until initiation of another anti-cancer therapy, disease progression, or study cut-off date, whichever comes first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 77 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, First-in-human, Dose Escalation Study of SAR440234 Administered as Single Agent by Intravenous Infusion in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), or High Risk Myelodysplasia (HR-MDS)
Actual Study Start Date : October 24, 2018
Estimated Primary Completion Date : November 2022
Estimated Study Completion Date : November 2022


Arm Intervention/treatment
Experimental: SAR440234
SAR440234 as weekly intravenous injection; a cycle is defined as 6 weeks of study treatment; (Additionally infusion on day 4 is planned for dose level ≥ 3). One dose escalation scheme will be used. Treatment may be continued as long as it is clinically beneficial.
Drug: SAR440234
Pharmaceutical form:lyophilisate to be resuspended in solution Route of administration: intravenous




Primary Outcome Measures :
  1. Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Baseline to Day 42 ]
    Incidence of DLTs observed, using NCI-CTCAE v4.03 or 2014 NCI Consensus Guidelines for cytokine release syndrome, during the first 42 days following the first administration of IMP in the first cycle of treatment.

  2. Incidence of allergic reactions/hypersensitivity and CRS/acute infusion reactions [ Time Frame: Baseline to 30 days after last study treatment administration ]
    Incidence of allergic reactions/hypersensitivity and CRS/acute infusion reactions

  3. Overall response rate (ORR) [ Time Frame: Baseline to 30 days after last study treatment administration ]
    ORR is defined as the proportion of patients with complete response (CR), CRi, and partial response (PR).

  4. Duration of response (DOR) [ Time Frame: Baseline to date of first documentation of disease progression ]
    DOR is defined as the time from the date of the first response (≥PR) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever happens first.

  5. Event-free survival [ Time Frame: Baseline to date of first documentation of disease progression ]
    Event-free survival is defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause.


Secondary Outcome Measures :
  1. Adverse events [ Time Frame: Baseline to 30 days after last study treatment administration ]
    Number of adverse events.

  2. Preliminary Anti-leukemia Activity [ Time Frame: Baseline to approximately 3 months after the last entered patient ]
    Preliminary anti-leukemia activity as defined by IWG for MDS or AML or National Comprehensive Cancer Network (NCCN) for B-ALL. (Dose escalation part).

  3. Immunogenicity of SAR440234 [ Time Frame: Baseline to approximately 3 months after the last entered patient ]
    Anti-SAR440234 Antibodies (ADA) incidence is defined as the proportion of patients found to either have treatment induced ADA or boosted their pre-existing ADA response during the study.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Confirmed diagnosis of Acute Myeloblastic leukemia (AML) (except acute promyelocytic leukemia), or myelodysplastic syndrome (MDS) with a risk category of intermediate or higher. Patients must have exhausted available treatment options and must not be eligible for any treatment known to provide clinical benefit.
  • Patients with AML must have relapsed or refractory disease that has been resistant to available therapies.
  • Patients with B-ALL (B acute lymphoid leukemia) in second or subsequent relapse: should have completed previously ≥1 cycle of a salvage regimen. Patients must have exhausted available treatment options and must not be eligible for any treatment known to provide clinical benefit.
  • Patients with HR-MDS (high risk myelodysplastic syndrome) must have >10% blasts in the bone marrow at the time of enrollment and fit one of the following categories: Not eligible for induction therapy and having completed ≥2 cycles of therapy or not eligible for allogeneic stem cell transplant and having completed ≥1 course of induction therapy.
  • Signed written informed consent.

Exclusion criteria:

  • Age <16 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status >2.
  • Patients with inadequate biological tests.
  • White blood cell count > 30,000/mm3
  • History of active or chronic autoimmune conditions that has required or requires therapy.
  • Graft-versus-host disease following allogeneic stem cell transplantation requiring treatment with more than 10 mg of oral prednisone or equivalent daily. The stem cell transplant and/or donor lymphocyte infusion should have been performed more than 3 months before study treatment start.
  • Second primary malignancy that requires active therapy. Adjuvant hormonal therapy is allowed.
  • Previous treatment with radiotherapy or immunotherapeutic agents in the 4 weeks prior to investigational medicinal product (IMP) administration.
  • Previous treatment with any other investigational agent in the 4 weeks prior to IMP administration.
  • Receiving, at the time of first IMP administration, of concurrent steroids >10 mg/day of oral prednisone or the equivalent for ≥3 months.
  • Requirement for tocilizumab for any other diagnosis.
  • Evidence of active central nervous system leukemia at the time of enrollment.
  • Acquired immunodeficiency syndrome (AIDS-related illnesses) or HIV (human immunodeficiency virus) disease requiring antiretroviral treatment or having active Hepatitis B viral infection or Hepatitis C viral infection.
  • Women of childbearing potential, male with a partner of childbearing potential who do not agree to use effective methods of birth control.
  • Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03594955


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

Locations
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United States, Texas
Investigational Site Number 8400001 Recruiting
Houston, Texas, United States, 77030
France
Investigational Site Number 2500004 Recruiting
Marseille, France, 13273
Investigational Site Number 2500001 Recruiting
Paris Cedex 10, France, 75010
Investigational Site Number 2500003 Recruiting
Villejuif Cedex, France, 94805
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03594955    
Other Study ID Numbers: TED15138
2017-004148-39 ( EudraCT Number )
U1111-1197-8041 ( Other Identifier: UTN )
First Posted: July 20, 2018    Key Record Dates
Last Update Posted: February 20, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid