Clinical trial NCT03860844: Isatuximab in Combination With Chemotherapy in Pediatric Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Keywords: Anti-CD38 monoclonal antibody
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-03-04
Enrollment: 67
Sex: ALL
Minimum age (years): 28
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objective:

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
* Relationship between clinical effects and CD38 receptor density and occupancy

Detailed description: The study included:

* a screening period of up to (up to 3 weeks prior to the first study treatment administration);
* a study treatment period \[Day 1 to Day 57 for Acute Lymphoblastic Leukemia (ALL); Day 1 to Day 22 for Acute Myeloid Leukemia (AML)\];
* the period of aplasia followed by a recovery period;
* an end of treatment (EOT) visit \[within 30 days after hematological recovery;
* a follow-up period (until final analysis cut off date).

Eligibility criteria: Inclusion criteria:

* Participant 28 days to less than 18 years of age, at the time of signing the informed consent.
* Participants must have had 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 have been previously treated for their disease and have relapsed or are refractory to most recent treatment. Participants in first or second relapse were eligible regardless of the remission duration.
* Participants who had no more than 1 prior salvage therapy.
* White Blood Cell (WBC) counts below 20 x10\^9/L on Day 1 before isatuximab administration

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. Exceptions were participants who needed to receive cytoreductive chemotherapy in order to decrease tumor burden (the study treatment may have started 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 \<5%.
* Participants with Burkitt-type ALL.
* Acute leukemia with testicular or central nerve system involvement alone.
* Participants who had developed therapy related acute leukemia.
* Live vaccine(s) within 30 days prior to the first IMP administration or plans to receive such vaccines during the study until 90 days after the last IMP administration.
* Participants with white blood cell count \> 50 x10\^9/L at the time of screening visit.
* Participants who had been exposed to anti-CD38 therapies within 6 months prior to Day-1.

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

Primary outcomes:
measure: Percentage of Participants With Complete Response (CR) Rate
timeFrame: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort)
measure: Number of Participants With Infusion Reactions (IRs)
timeFrame: From the time of the first treatment administration (Day 1) up to 30 days after the last treatment (maximum duration of exposure of 13.1 weeks for B-ALL cohort, 10.7 weeks for T-ALL cohort and 7.1 weeks for AML cohort)
measure: B-ALL and T-ALL: Area Under the Concentration Time Curve (AUC) of Isatuximab
timeFrame: From Week 0 to Week 1, Week 0 to Week 5, and Week 0 to Week 10
measure: AML: AUC of Isatuximab
timeFrame: From Week 0 to Week 1, Week 0 to Week 3, and Week 0 to Week 8
measure: B-ALL and T-ALL: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
timeFrame: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 22, Cycle 1 Day 29, Cycle 2 Day 43, Cycle 2 Day 57
measure: AML: Plasma Concentration Reached by Isatuximab Before Next Dose Administration (Ctrough)
timeFrame: Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15
measure: B-ALL and T-ALL: Concentrations at the End of Infusion (Ceoi) of Isatuximab
timeFrame: At end of infusion on Cycle 1 Days 1 and 29
measure: AML: Ceoi of Isatuximab
timeFrame: At end of infusion on Cycle 1 Days 1 and 15
measure: Number of Participants With Negative Minimal Residual Disease (MRD)
timeFrame: From screening until the study completion date, approximately 45 months
measure: Overall Response Rate (ORR)
timeFrame: From enrollment until the primary analysis completion date of 12 Sep 2022; the median duration of exposure was approximately 7 weeks
measure: Overall Survival (OS)
timeFrame: From first study treatment administration up to death due to any cause, a maximum of 45 months
measure: Event-Free Survival (EFS)
timeFrame: From study treatment administration up to the date of first documented disease progression or death due to any cause, a maximum of 45 months
measure: Duration of Response (DoR)
timeFrame: From first documented response up to the date of first documented disease progression or death due to any cause, a maximum of 45 months
measure: Cluster of Differentiation (CD)38 Receptor Density
timeFrame: Pre-dose on Day 1
measure: CD38 Receptor Occupancy
timeFrame: Pre-dose on Day 15
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Sarah Cannon Research Institute-Site Number:8400001
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center of Dallas-Site Number:8400002
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number :0320002
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Investigational Site Number :0320006
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320005
city: Buenos Aires
country: Argentina
facility: Investigational Site Number :0320004
city: Curitiba
country: Brazil
facility: Investigational Site Number :0760013
state: Paraná
city: Curitiba
country: Brazil
facility: Investigational Site Number :0760006
state: Paraná
city: Porto Alegre
country: Brazil
facility: Investigational Site Number :0760007
state: Rio Grande Do Sul
city: Jau
country: Brazil
facility: Investigational Site Number :0760010
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Investigational Site Number :0760009
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Investigational Site Number :0760001
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Investigational Site Number :0760004
state: São Paulo
city: Copenhagen
country: Denmark
facility: Investigational Site Number :2080001
city: Lille
country: France
facility: Investigational Site Number :2500002
city: Lyon
country: France
facility: Investigational Site Number :2500003
city: PARIS Cedex 12
country: France
facility: Investigational Site Number :2500001
city: PARIS Cedex 19
country: France
facility: Investigational Site Number :2500004
city: Erlangen
country: Germany
facility: Investigational Site Number :2760005
city: Hamburg
country: Germany
facility: Investigational Site Number :2760003
city: Münster
country: Germany
facility: Investigational Site Number :2760006
city: Athens
country: Greece
facility: Investigational Site Number :3000001
city: Budapest
country: Hungary
facility: Investigational Site Number :3480002
city: Genova
country: Italy
facility: Investigational Site Number :3800002
state: Liguria
city: Monza
country: Italy
facility: Investigational Site Number :3800001
state: Lombardia
city: Torino
country: Italy
facility: Investigational Site Number :3800003
state: Piemonte
city: Verona
country: Italy
facility: Investigational Site Number :3800005
state: Veneto
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number :4100004
state: Seoul-teukbyeolsi
city: Monterrey
country: Mexico
facility: Investigational Site Number :4840001
state: Nuevo León
city: Col. Rancho Menchaca
country: Mexico
facility: Investigational Site Number :4840005
state: Querétaro
city: Utrecht
country: Netherlands
facility: Investigational Site Number :5280001
city: Bergen
country: Norway
facility: Investigational Site Number :5780001
city: Oslo
country: Norway
facility: Investigational Site Number :5780002
city: Arequipa
country: Peru
facility: Investigational Site Number :6040001
city: Lima
country: Peru
facility: Investigational Site Number :6040002
city: Coimbra
country: Portugal
facility: Investigational Site Number :6200002
city: Lisboa
country: Portugal
facility: Investigational Site Number :6200001
city: Porto
country: Portugal
facility: Investigational Site Number :6200003
city: Göteborg
country: Sweden
facility: Investigational Site Number :7520001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: