None listed
Conditions
Interventions
Isatuximab Type of group
Study intervention is defined as isatuximab and salvage chemotherapy intended to be
administered to a study participant according to the study protocol. For chemotherapy, the body
surface area used for dose determination is capped at 2 m2
AML cohort: 20 mg/kg weekly (this could be
modified based on modeling and PK assessment
on the first 20 participants) Days 1, 8, and 15
(mandatory for Cycles 1 and 2).
ALL cohorts: 20 mg/kg weekly (this could be
modified based on modelin
Sponsors
Sanofi Aventis Recherche & Development,
Eligibility
Inclusion criteria
Inclusion criteria: INCLUSION CRITERIA Participants are eligible to be included in the study only if all of the following criteria apply: 01. Age Participant must be 28 days to less than 18 years of age at the time of the signing of the informed consent. Participants under 2 years of age can only be enrolled after the dose reassessment is completed on the first 20 participants who are 2 to less than 18 years of age (see Section 4.3 and Section 9.5). 02. Type of participant and disease characteristics Participants must have a confirmed diagnosis of relapsed ALL of T- or B-cell origin including lymphoblastic lymphoma (LBL, or relapsed AML (excluding M3 type: acute promyelocytic leukemia) including participants with history of myelodysplasia (MDS). 03. Sex A) Male participants: A male participant with a female partner of childbearing potential must agree to use contraception as detailed in Appendix 4 (Section 10.4) of this protocol during the treatment period and for at least 6 months after the last dose of isatuximab, or 12 months after the last dose of cyclophosphamide and refrain from donating sperm during this period. B) Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 4 [Section 10.4]), not breastfeeding, and at least one of the following conditions applies: 04. Informed Consent The participant who has reached legal age of majority as defined by local regulation or the parent(s)/legal guardian(s) must provide signed informed consent prior to any study-related procedures being performed. If the participant is legally a minor per local regulations, assent shall be obtained from the participant, if applicable.
Exclusion criteria
Exclusion criteria: EXCLUSION CRITERIA Participants are excluded from the study if any of the following criteria apply: Medical conditions 01. Evidence of ongoing infection or seropositivity for human immunodeficiency virus (HIV), or active hepatitis B (defined as either positive hepatitis B surface [HBs] antigen or positive hepatitis B viral deoxyribonucleic acid [DNA] test above the lower limit of detection of the assay), or hepatitis C infection. Presence of positive hepatitis B core (HBc) antibody in the presence of a negative HBs antigen test or a negative hepatitis B viral DNA test in serum indicates a prior infection without currently active hepatitis or carrier status and is not an exclusion criterion. Human immunodeficiency virus, hepatitis B, and hepatitis C virus serology testing to be performed and collected in database only in countries where requested by local regulations. E 02. Second malignancy other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma, unless they are successfully treated with curative intent for more than 3 years before entering the study. E 03. Cardiomyopathy New York Heart Association Grade 3 or 4. E 04. History of thrombophilic disease, allergic to asparaginase for participants with ALL, or prior intolerance (ie, serious thrombosis, pancreatitis, or hemorrhagic events). E 05. Eastern Cooperative Oncology Group (ECOG) performance status >2 or Lansky score 2.5 × upper limit of normal (ULN) unless the participant has Gilbert’s syndrome or elevation related to acute leukemia. E 07. Alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase >5 × ULN, unless considered due to the disease. E 08. Serum creatinine >2 × ULN and/or estimated glomerular filtration rate (eGFR) 2 weeks and must have recovered from acute toxicity (ie, to Grade 1 or less except alopecia or peripheral neuropathy Grade ≤2 without pain) before the first study intervention administration. The study treatment may start earlier if necessitated by the participant´s medical condition (eg, rapidly progressive disease) following discussion with the Sponsor. E 11. 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 intervention administration. Prior/concurrent clinical study experience E 12. Intolerance or contraindication to treatment with mAb or any other drug part of the study intervention. Other exclusion criteria are described in protocol section 5.2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The primary efficacy endpoint is the morphological CR rate, defined as the proportion of participants with CR or CRi. The CR rate will be summarized with descriptive statistics on the all evaluable population. An 80% confidence interval will be computed using the Clopper-Pearson method. Measure:Morphological CR rate is defined as the proportion of participants with CR or CRi, in AML, B-ALL, and T-ALL cohorts. Timepoints:Data from participants enrolled in 3 cohorts (T-ALL, B-ALL, and AML) will be analyzed separately. Unless otherwise specified, analyses will be descriptive and performed on the AT population, except for the analyses of efficacy endpoints that will utilize the evaluable population. The baseline for a given parameter is defined as the last assessment for this parameter before the first study intervention administration. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Pretreatment AEs are defined as any AE during the screening period. Treatment-emergent AEs are defined as AEs that develop, worsen (according to the Investigator opinion) or become serious during the on-treatment period. The primary focus of AE reporting will be on TEAEs. Post-treatment AEs are defined as AEs that are reported during the post-treatment period. Related AEs and any SAE ongoing at the end of treatment must be followed until resolution or stabilization. Any AEs or SAEs assessed as related to IMP that are new during the follow-up period will be reported and followed until recovery or stabilization. Measure:Safety assessment, in terms of AEs/SAEs. In addition, laboratory data, vital signs, and physical examination will be assessed throughout the study. Timepoints:Throughout the study | — |
Countries
Argentina, Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Korea South, Mexico, Nederland, Norway, Peru, Portugal, Sweden, United States
Contacts
Public ContactMiguel Angel Noel
SANOFI AVENTIS DEL PERU S.A.
Outcome results
None listed