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Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03860844
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : August 29, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To evaluate the anti-leukemic activity of isatuximab in combination with standard chemotherapies in pediatric participants of ages 28 days to less than 18 years with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Acute Myeloid Leukemia (AML)

Secondary Objectives:

  • Safety and tolerability assessments
  • Assessment of infusion reactions (IRs)
  • Pharmacokinetics (PK) of isatuximab
  • Minimal residual disease
  • Overall response rate
  • Overall survival
  • Event free survival
  • Duration of response

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Drug: Isatuximab SAR650984 Drug: Dexamethasone Drug: Fludarabine Drug: Cytarabine Drug: Liposomal daunorubicin Drug: Daunorubicin Drug: Idarubicin Drug: Filgrastim Drug: Mitoxantrone Drug: Doxorubicin Drug: Vincristine Drug: PEG Asparaginase Drug: Cyclophosphamide Drug: Etoposide Drug: Methotrexate Phase 2

Detailed Description:
The study will include a screening period of up to 21 days (Day -21 to -1), a study treatment period [Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute Myeloid Leukemia (AML)], a recovery period (until an end of treatment visit [within 30 days after hematological recovery]) and a follow-up period (until final analysis cut off date).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of Isatuximab Used in Combination With Chemotherapy in Pediatric Patients From 28 Days to Less Than 18 Years of Age With Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse
Actual Study Start Date : August 6, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: AML cohort or ALL cohort

Acute Myeloid Leukemia (AML) cohort: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle.

Acute Lymphoblastic Leukemia (ALL) cohort: Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.

Drug: Isatuximab SAR650984
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Dexamethasone
Pharmaceutical form: Solution for injection or tablet Route of administration: Intravenous or oral

Drug: Fludarabine
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Cytarabine
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Liposomal daunorubicin
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Daunorubicin
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Idarubicin
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Filgrastim
Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Drug: Mitoxantrone
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Doxorubicin
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Vincristine
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: PEG Asparaginase
Pharmaceutical form: Solution for injection Route of administration: Intramuscular

Drug: Cyclophosphamide
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Etoposide
Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: Methotrexate
Pharmaceutical form: Solution for injection Route of administration: Intravenous




Primary Outcome Measures :
  1. Complete Response (CR) rate in acute myeloid leukemia (AML) cohort [ Time Frame: Baseline to Day 22 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi (CR with incomplete peripheral recovery)

  2. Complete Response (CR) rate in B-cell acute lymphoblastic leukemia (B-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi

  3. Complete Response (CR) rate in T-cell acute lymphoblastic leukemia (T-ALL) cohort [ Time Frame: Baseline to Day 57 ]
    Morphological CR rate defined as the proportion of participants with CR or CRi


Secondary Outcome Measures :
  1. Safety and tolerability assessments: Adverse events [ Time Frame: Baseline to approximately 3 months ]
    Number of adverse events and serious adverse events

  2. Assessment of infusion reactions [ Time Frame: Time from isatuximab infusion to resolution (approximately 2 days) ]
    Incidence and severity of infusion reactions

  3. Pharmacokinetics of isatuximab: Cmax [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Maximum observed concentration (Cmax)

  4. Pharmacokinetics of isatuximab: Ctrough [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough)

  5. Pharmacokinetics of isatuximab: AUC [ Time Frame: Day 1 to 30 days after hematological recovery ]
    Partial area under the serum concentration time curve: AUC

  6. Minimal residual disease [ Time Frame: On day 43 ]
    Estimation of minimal residual disease in participants achieving CR or CRi

  7. Overall response rate [ Time Frame: On day 43 ]
    The overall response rate is defined as the proportion of participants with CR or CRi for blood and bone marrow disease; Partial response (PR) based on the National Comprehensive Cancer Network (NCCN) guideline will be considered in case of lymphomatous extramedullary disease for T-ALL participants

  8. Overall survival [ Time Frame: Baseline to approximately 3 months ]
    Overall survival is defined as the time interval from the date of first study treatment administration to death from any cause

  9. Event free survival [ Time Frame: Baseline to approximately 3 months ]
    Event free survival is defined as the time interval from the date of first study treatment administration to the date of the first of: completion or going off protocol induction/consolidation therapy without CR, relapse from CR, or death due to any cause

  10. Duration of response [ Time Frame: Time from the first response to the first disease progression or death, up to Month 42 ]
    Duration of response is defined as the time from the date of the first response to the date of first disease progression or death from any cause, whichever happens first



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Participant must be 28 days to less than 18 years of age, at the time of signing the informed consent.
  • Participants must have a confirmed diagnosis of relapsed Acute Lymphoblastic Leukemia (ALL) of T- or B-cell origin including T-lymphoblastic lymphoma (LBL), or relapsed Acute Myeloblastic Leukemia (AML) including participants with history of myelodysplasia.
  • Participants must be previously treated for their disease and have relapsed or are refractory to most recent treatment. Participants in first or second relapse will be eligible regardless of the remission duration.
  • Participants with no more than 1 prior salvage therapy.

Exclusion criteria:

  • Any serious active disease or co-morbid condition which, in the opinion of the Investigator, may interfere with the safety of the study treatment or the compliance with the study protocol.
  • Participants must have been off prior treatment with immunotherapy/investigational agents and chemotherapy for >2 weeks and must have recovered from acute toxicity before the first study treatment administration. Treatment may start earlier if necessitated by the patient's medical condition (eg, rapidly progressive disease) following discussion with the Sponsor.
  • Prior stem cell transplant within 3 months and/or evidence of active systemic Graft versus Host Disease (GVHD) and/or immunosuppressive therapy for GVHD within 1 week before the first study treatment administration.
  • Participants with LBL with bone marrow blasts <20%.
  • Participants with Burkitt-type ALL.
  • Acute leukemia with testicular or central nerve system involvement alone.
  • Participants who have developed therapy related acute leukemia.

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): NCT03860844


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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Denmark
Investigational Site Number 2080001 Recruiting
København Ø, Denmark, 2100
Finland
Investigational Site Number 2460001 Recruiting
Tampere, Finland, 33520
Norway
Investigational Site Number 5780001 Recruiting
Bergen, Norway, 5021
Investigational Site Number 5780002 Recruiting
Oslo, Norway, 0342
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: NCT03860844     History of Changes
Other Study ID Numbers: ACT15378
PIP - 2018‐002697‐45
U1111-1202-1096 ( Other Identifier: UTN )
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
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.: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Cyclophosphamide
Doxorubicin
Methotrexate
Fludarabine
Etoposide
Vincristine
Daunorubicin
Mitoxantrone
Idarubicin
Asparaginase
Pegaspargase
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents