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

Sponsor

Sanofi (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03860844

Collaborator

(none)

Enrollment

Locations

Arm

48.8

Anticipated Duration (Months)

1.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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
Relationship between clinical effects and CD38 receptor density and occupancy

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia Acute Myeloid Leukemia	Drug: Montelukast Drug: Isatuximab 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 Drug: L - Asparginase Drug: Hydroxyurea Drug: L - Asparaginase (Erwinase) Drug: Tocilizumab	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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

N/A

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 :

Aug 6, 2019

Anticipated Primary Completion Date :

Aug 31, 2023

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.	Drug: Montelukast Pharmaceutical form: tablet Route of administration: oral Drug: Isatuximab Pharmaceutical form: Solution for injection Route of administration: Intravenous Other Names: SAR650984 Sarclisa 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: Intravenous 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: Intravenous 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 Drug: L - Asparginase Pharmaceutical form: Solution for injection Route of administration: Intramuscular Drug: Hydroxyurea Pharmaceutical form: Solution for injection Route of administration: Intravenous Drug: L - Asparaginase (Erwinase) Pharmaceutical form: Solution for injection Route of administration: Intramuscular Drug: Tocilizumab Pharmaceutical form: Solution for injection Route of administration: Intravenous

Arm

Intervention/Treatment

Experimental: Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia

This arm includes participants from 3 cohorts: AML, T-ALL and B-ALL.; AML: Weekly dosing of isatuximab with induction chemotherapy. The therapy may be repeated one more cycle; ALL: (Includes T-ALL and B-ALL) Weekly dosing of isatuximab with induction chemotherapy, then biweekly dosing of isatuximab with consolidation chemotherapy.

Drug: Montelukast

Pharmaceutical form: tablet Route of administration: oral

Drug: Isatuximab

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Other Names:

SAR650984

Sarclisa

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: Intravenous

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: Intravenous

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

Drug: L - Asparginase

Pharmaceutical form: Solution for injection Route of administration: Intramuscular

Drug: Hydroxyurea

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Drug: L - Asparaginase (Erwinase)

Pharmaceutical form: Solution for injection Route of administration: Intramuscular

Drug: Tocilizumab

Pharmaceutical form: Solution for injection Route of administration: Intravenous

Outcome Measures

Primary Outcome Measures

Complete Response (CR) rate in acute myeloid leukemia (AML) cohort [Baseline to Day 22]
CR rate is defined as the proportion of participants with CR or CRi, in AML
Complete Response (CR) rate in B-cell acute lymphoblastic leukemia (B-ALL) cohort [Baseline to Day 57]
Morphological CR rate defined as the proportion of participants with CR or CRi
Complete Response (CR) rate in T-cell acute lymphoblastic leukemia (T-ALL) cohort [Baseline to Day 57]
Morphological CR rate defined as the proportion of participants with CR or CRi

Secondary Outcome Measures

Safety and tolerability assessments [Baseline to approximately 3 months]
Number of adverse events and serious adverse events
Assessment of infusion reactions [Time from isatuximab infusion to resolution (approximately 2 days)]
Incidence and severity of infusion reactions
Pharmacokinetics of isatuximab: Cmax [Day 1 to 30 days after hematological recovery]
Maximum observed concentration (Cmax)
Pharmacokinetics of isatuximab: Ctrough [Day 1 to 30 days after hematological recovery]
Concentration observed just before treatment administration during repeated dosing (Ctrough)
Pharmacokinetics of isatuximab: AUC [Day 1 to 30 days after hematological recovery]
Partial area under the serum concentration time curve: AUC
Minimal residual disease [On day 43]
Estimation of minimal residual disease in participants achieving CR or CRi
Overall response rate [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
Overall survival [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
Event free survival [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
Duration of response [Time from the first response to the first disease progression or death]
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
Change in CD38 receptor density and occupancy [Baseline to Day 15]
CD38 receptor density will be assessed at baseline and CD38 receptor occupancy at Day 15 and correlated with clinical endpoints.

Eligibility Criteria

Criteria

Ages Eligible for Study:

28 Days to 17 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
WBC counts below 20 x109/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 are participants who need to receive cytoreductive chemotherapy in order to decrease tumor burden (the study 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 <5%.
Participants with Burkitt-type ALL.
Acute leukemia with testicular or central nerve system involvement alone.
Participants who have 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 x109/L at the time of screening visit.
Participants who have been exposed to anti-CD38 therapies within 6 months prior to Day-1.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :8400004	Cincinnati	Ohio	United States	45229-3039
2	Investigational Site Number :8400001	Nashville	Tennessee	United States	37203
3	Investigational Site Number :8400002	Dallas	Texas	United States	75235
4	Investigational Site Number :8400003	Seattle	Washington	United States	98040
5	Investigational Site Number :0320002	Caba	Buenos Aires	Argentina	C1181ACH
6	Investigational Site Number :0320003	Caba	Buenos Aires	Argentina	C1270AAN
7	Investigational Site Number :0320006	Capital Federal	Buenos Aires	Argentina	C1425DUC
8	Investigational Site Number :0320005	Buenos Aires		Argentina	1118
9	Investigational Site Number :0320004	Buenos Aires		Argentina	C1245AAM
10	Investigational Site Number :0320001	Córdoba		Argentina	X5000JHQ
11	Investigational Site Number :0560001	Leuven		Belgium	3000
12	Investigational Site Number :0760013	Curitiba	Paraná	Brazil	80250-060
13	Investigational Site Number :0760006	Curitiba	Paraná	Brazil	81520-060
14	Investigational Site Number :0760007	Porto Alegre	Rio Grande Do Sul	Brazil	90035 003
15	Investigational Site Number :0760010	Jau	São Paulo	Brazil	17210-070
16	Investigational Site Number :0760009	Ribeirão Preto	São Paulo	Brazil	14051-140
17	Investigational Site Number :0760004	Sao Paulo	São Paulo	Brazil	04039-001
18	Investigational Site Number :0760001	Sao Paulo	São Paulo	Brazil	08270-070
19	Investigational Site Number :1240001	Vancouver	British Columbia	Canada	V6H3V4
20	Investigational Site Number :2030002	Brno		Czechia	62500
21	Investigational Site Number :2030001	Praha 5 - Motol		Czechia	15006
22	Investigational Site Number :2080001	Copenhagen		Denmark	2100
23	Investigational Site Number :2500005	Bordeaux		France	33000
24	Investigational Site Number :2500002	Lille		France	59000
25	Investigational Site Number :2500003	Lyon		France	69008
26	Investigational Site Number :2500001	PARIS Cedex 12		France	75571
27	Investigational Site Number :2500004	PARIS Cedex 19		France	75935
28	Investigational Site Number :2760005	Erlangen		Germany	91054
29	Investigational Site Number :2760001	Essen		Germany	45147
30	Investigational Site Number :2760004	Halle (Saale)		Germany	06120
31	Investigational Site Number :2760003	Hamburg		Germany	20246
32	Investigational Site Number :2760006	Münster		Germany	48149
33	Investigational Site Number :3000001	Athens		Greece	115 27
34	Investigational Site Number :3480002	Budapest		Hungary	1094
35	Investigational Site Number :3480001	Debrecen		Hungary	4032
36	Investigational Site Number :3800001	Monza	Lombardia	Italy	20900
37	Investigational Site Number :3800002	Genova		Italy	16147
38	Investigational Site Number :3800004	Roma		Italy	00165
39	Investigational Site Number :3800003	Torino		Italy	10126
40	Investigational Site Number :3800005	Verona		Italy	37126
41	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03080
42	Investigational Site Number :4100003	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03722
43	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	06351
44	Investigational Site Number :4100004	Seoul	Seoul-teukbyeolsi	Korea, Republic of	137-701
45	Investigational Site Number :4840005	Queretaro	Querétaro	Mexico	76140
46	Investigational Site Number :4840001	Monterrey, Nuevo León		Mexico	64460
47	Investigational Site Number :5280001	Utrecht		Netherlands	3584
48	Investigational Site Number :5780001	Bergen		Norway	5021
49	Investigational Site Number :5780002	Oslo		Norway	0342
50	Investigational Site Number :6040001	Arequipa		Peru
51	Investigational Site Number :6040002	Lima		Peru	LIMA 34
52	Investigational Site Number :6200002	Coimbra		Portugal	3000-076
53	Investigational Site Number :6200001	Lisboa		Portugal	1099-023
54	Investigational Site Number :6200003	Porto		Portugal	4200-162
55	Investigational Site Number :7520001	Göteborg		Sweden	416 85