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

Sanofi

Status and phase

Terminated

Phase 2

Conditions

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia

Treatments

Drug: Fludarabine

Drug: Etoposide

Drug: Daunorubicin (nonliposomal)

Drug: Idarubicin

Drug: Hydroxyurea

Drug: Dexamethasone or equivalent

Drug: Mitoxantrone

Drug: Cytarabine

Drug: Cyclophosphamide

Drug: L - Asparginase

Drug: Doxorubicin

Drug: Pegaspargase (PEG) Asparaginase

Drug: Methotrexate

Drug: Liposomal daunorubicin

Drug: L - Asparaginase (Erwinase)

Drug: Vincristine

Drug: Isatuximab

Drug: Filgrastim or equivalent

Study type

Interventional

Funder types

Industry

Identifiers

NCT03860844

PIP - 2018-002697-45

U1111-1202-1096 (Other Identifier)

2018-002697-45 (EudraCT Number)

ACT15378

Details and patient eligibility

About

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

Full 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).

Enrollment

67 patients

Sex

All

Ages

28 days to 17 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

67 participants in 1 patient group

Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia

Experimental group

Description:

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.

Treatment: