The safety and efficacy of the medicine Inotuzumab Ozogamicin in children with relapsed/refractory acute lymphatic leukemia (ALL)

Phase 1

• Conditions: pediatric CD22-positive relapsed/refractory Acute Lymphoblastic Leukemia; MedDRA version: 21.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-000227-71-SE
• Lead Sponsor: Erasmus Medical Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-02-15
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 156

Inclusion Criteria

Eligibility:
Age for all strata (Str1A, ph2, Str1B, Str2 and Str3): Patients must be =
1 and < 18 years of age

Patients with Down syndrome are excluded in Stratum 1A and 1B/1B-ASP but not in the phase 2 cohort and Stratum 3.

Additional criteria for Stratum 1A and 1B
•First 3 patients on dose level 1 must be 6-18 yrs.
•Then at least 2 additional patients must be enrolled from age 1-6 yrs at
the same dose level.
•After this: subsequent dose levels may enroll patients aged 1-18 yrs.
•In case 2 younger patients are not yet recruited, patients aged 6-18yrs
may continue to be enrolled at dose level 1 until a maximum of 6
patients are enrolled.

Stratum 1A, phase 2 and stratum 1B/1B-ASP: Diagnosis
Patients must have either 1st relapsed BCP-ALL after allo-HSCT or 2nd or
greater relapsed or refractory BCP-ALL, or refractory disease (after at
least 2 prior regimens):
•M2 or M3 marrow status (= 5% blasts by morphology)
•CD22 surface antigen positive (either BM or PB)
•Stratum 1 only: The first 6 patients must have M3 marrow status (=
25% blasts by morphology).

Stratum 2: Diagnosis
Patients must have 2nd or greater relapsed or refractory CD22-positive B-cell malignancy including but not limited to diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma
(PMBCL), Burkitt lymphoma, Burkitt leukemia or B-cell precursor
lymphoblastic lymphoma:
•Histologic verification of disease at original diagnosis or subsequent
relapse
•Evaluable or measurable disease (by radiographic criteria or BM
disease present)
• CD22 surface antigen positive (either biopsy material, BM or PB)

Str3: diagnosis:
• 1st BM or combined relapse of CD22+ VHR BCP-ALL defined as:
- any relapse <18 months from initial diagnosis and/or
- cytogenetic-high risk characteristics: KTM2A/AF4, E2A/TCF3-PBX1
t(1;19) or E2A/TCF3-HLF t(17;19), hypodiploidy (less than 40
chromosomes), TP53 mutation and/or deletion
• excluding patients transplanted in 1st CR.
• M2 or M3 marrow status (= 5% blasts by morphology)
• CD22 surface antigen positive (in either the BM or PB)
• Evidence of prior fusion gene abnormalities is acceptable
• cytogenetic-high risk characteristics determined by chromosome
banding analysis (CBA), FISH, PCR and/or Next Generation Sequencing

All strata:
Performance Level and Life Expectancy:
•Karnofsky > 60% (patients >16 yrs) or Lansky >60% (patients =16
yrs)
•life expectancy of at least 6 weeks.

Prior Therapy:
…
Renal and Hepatic Function:
•serum creatinine = 1.5 x ULN according to age. If serum creatinine is >
than 1.5 x ULN, the patient must have a GFR =
70mL/min/1.73m2.
•AST and ALT = 2.5 x ULN.
•total bilirubin = 1.5 x ULN (unless patient has documented Gilbert
syndrome &AST and ALT are <=2.5 x ULN).
Cardiac Function:
•shortening fraction = 30% by ECG or an ejection fraction > 50% by
MUGA.
Reproductive Function:
•If applicable, negative urine or serum pregnancy test confirmed prior to
enrollment.
•If applicable, agree not to breastfeed while on this study.
•If applicable, agree using effective method of contraception during the
study and for 5 months (male patients) or 8 months (female patients) after the last dose of InO.

Are the trial subjects under 18? yes
Number of subjects for this age range: 156
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Concurrent disease:
•Patients will be excluded if they have significant concurrent disease,
illness, psychiatric disorder or social issue that would compromise
patient safety or compliance with protocol therapy, interfere with
consent, study participation, follow up, or interpretation of study results.
•Patients with Down syndrome are excluded in the dose finding
parts (stratum 1A and 1B), but not in the phase 2 cohort or VHR cohort.

Additional exclusion criteria for Stratum 1B:
• Patients with grade 3-4 peripheral neuropathy (as defined in the
Delphi consensus of acute toxic effects for childhood ALL by
Schmiegelow et al.1 ). Patients with prior history of thrombosis during
steroid and/or asparaginase are eligible provided they use adequate
anti-coagulant prophylaxis, according to institutional guidelines.
• Patients in whom prior experience suggests that a timely delivery of
therapy is unlikely or associated with an undue risk because of
intolerance.

Additional exclusion criteria for Stratum 1B-ASP cohort only
-Patients with any history of PEG-asparaginase intolerance due to
allergic reactions or silent inactivation during prior treatment.
• Patients with any history of prior asparaginase-associated acute
pancreatitis (any grade as defined in the Delphi consensus.1).
Patients who are excluded from Stratum 1B-ASP may potentially be
enrolled in Stratum 1B expansion cohort.

Additional exclusion criteria for Stratum 3 (VHR cohort) only:
• Patients who are transplanted in CR1 (such patients are eligible for
the phase 1B cohort).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified