A study with Inotuzumab Ozogamicin (shortened to InO) vs. ALLR3 (a multi-agent chemotherapy) for the treatment of pediatric leukemia

Austria, Belgium, Czech Republic, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Israel, Italy, Netherlands, Norway, Poland, Slovakia, Spain, Sweden, Switzerland (ICTRP)

Identifiant de l'essai ICTRP
EUCTR2022-000186-40 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
A PROSPECTIVE, RANDOMIZED, OPEN-LABEL PHASE 2 STUDY TO EVALUATE THE SUPERIORITY OF INOTUZUMAB OZOGAMICIN MONOTHERAPY VERSUS ALLR3 FOR INDUCTION TREATMENT OF CHILDHOOD HIGH RISK FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKAEMIA (BASEC)

Titre académique
A PROSPECTIVE, RANDOMIZED, OPEN-LABEL PHASE 2 STUDY TO EVALUATE THE SUPERIORITY OF INOTUZUMAB OZOGAMICIN MONOTHERAPY VERSUS ALLR3 FOR INDUCTION TREATMENT OF CHILDHOOD HIGH RISK FIRST RELAPSE B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKAEMIA - A Ph2 Superiority Study with InO Monotherapy vs ALLR3 for Induction Treatment of Childhood HR ALL (ICTRP)

Titre public
A study with InO vs. ALLR3 in treating childhood leukemia (ICTRP)

Maladie en cours d'investigation
Acute Lymphoblastic Leukemia (ALL)
MedDRA version: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps);Therapeutic area: Diseases [C] - Cancer [C04] (ICTRP)

Intervention étudiée

Trade Name: Besponsa
Product Name: Besponsa
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: INOTUZUMAB OZOGAMICIN
CAS Number: 635715-01-4
Current Sponsor code: PF-05208773
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Product Name: Mitoxantrone hydrochloride
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: MITOXANTRONE HYDROCHLORIDE
CAS Number: 70476-82-3
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Product Name: Vincristine sulfate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine sulfate
CAS Number: 2068-78-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Product Name: Dexamethasone phosphate
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DEXAMETHASONE PHOSPHATE
CAS Number: 312-93-6
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 8-

Product Name: Dexamethasone phosphate
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone phosphate
CAS Number: 312-93-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Product Name: Dexamethasone phosphate
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone phosphate
CAS Number: 312-93-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Product Name: Dexamethasone phosphate
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone phosphate
CAS Number: 312-93-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Product Name: Pegaspargase
Pharmaceutical Form: Powder for solution (ICTRP)

Type d'essai
Interventional clinical trial of medicinal product (ICTRP)

Plan de l'étude
Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2 (ICTRP)

Critères d'inclusion/exclusion
Gender:
Female: yes
Male: yes

Inclusion criteria:
1. Male or female participants between 1 and less than 18 years of age.

Type of Participant and Disease Characteristics:
2. Morphologically confirmed diagnosis of first relapse HR BCP ALL;
HR first relapse is defined as relapse occurring within 18 to 30 months of original diagnosis of ALL or within 6 months of completion of primary therapy, and lacking any identified very high risk genetic abnormalities (ie, KMT2A-rearrangements, TCF3-HLF, TCF3-PBX1, hypodiploidy [<45
chromosomes], TP53 alteration)
? CD22-positive ALL as defined by local institution;
? Bone marrow involvement of = 5% leukemic blasts (= M2 status).

Other Inclusion Criteria:
3. Adequate serum chemistry parameters:
? An estimated glomerular filtration rate (eGFR) in participants 1 to less than 2 years of age, or estimated creatinine clearance (eCrCl) in those 2 to less than 18 years of age, =30 mL/min using the recommended formula
? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =5 ? institutional ULN at the time of randomization or pre-cytoreduction/general anesthesia;
? Total bilirubin =1.5 ? institutional ULN unless the participant has documented Gilbert?s syndrome;
4. Prior history of thrombosis during corticosteroid use and/or asparaginase are eligible provided the participant receives anti-coagulant prophylaxis per institutional guidelines.
5. Cardiac shortening fraction = 30% by echocardiogram or ejection fraction > 50% by MUGA.

Are the trial subjects under 18? yes
Number of subjects for this age range: 100
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
(ICTRP)

Exclusion criteria:
Medical Conditions:
1. Any history of:
? Prior or ongoing hepatic SOS or prior liver failure [defined as severe acute liver injury with encephalopathy and impaired synthetic function
(INR of =1.5)];
? Prior allo-HSCT or CAR T-cell therapy;
? Isolated extramedullary leukemia;
? Confirmed testicular relapse unless orchiectomy was performed prior to randomization;
? Philadelphia-chromosome positive ALL, ie. BCR-ABL/t(9;22) present;
? Presence of Grade 3 or Grade 4 peripheral neuropathy as defined in the Delphi consensus of acute toxic effects for childhood ALL;
? Hypersensitivity to the active ingredient of InO or any of its excipients;
? Hypersensitivity/allergy to PEG-ASP;
? Intolerance to any of the ALLR3 agents (mitoxantrone, vincristine, dexamethasone, asparaginase);
? Grade 3 or Grade 4 pancreatitis due to any cause, as defined by CTCAE v4.03;
? Grade 3 or Grade 4 allergic reaction to a monoclonal antibody;
? Participants not fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, defined as resolution of all such non-hematologic toxicities to Grade =2 per the NCI CTCAE v 4.03 prior to randomization, with the exception of the laboratory abnormalities as defined by other inclusion/exclusion criteria;
? Down syndrome;
? Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study;
? Charcot-Marie-Tooth disease.

2. Prior/Concomitant Therapy with:
? A calicheamicin-conjugated antibody (eg, InO or gemtuzumab ozogamicin) or prior therapy with a CD22-targeted therapy (immunotoxin or CAR T-cell therapy);
? Cytotoxic therapy within 7 days prior to enrollment, with the exception of hydroxyurea and corticosteroids which are permitted prior
to initiating study intervention. Participants may have received intrathecal chemotherapy at any time prior to study entry.
NOTE: No waiting period is required for participants who relapse while receiving first-line maintenance chemotherapy.
? Any radiation therapy within 28 days prior to enrollment;
? The last dose of granulocyte stimulating factor (ie, Neupogen or equivalent) administered within 7 days prior to study enrollment and the last dose of pegfilgrastim (Neulasta?) given within 14 days prior to enrollment;
? Less than 3 half-lives elapsed after the last dose of a mAb (eg, rituximab=66 days, epratuzumab=69 days). Participants must not have received blinatumomab within 4 weeks before study enrollment;
? Current use of any prohibited concomitant medication(s) or participants unwilling/unable to use a permitted concomitant medication(s);
? Any vaccination with live viral vaccines within 2 weeks of the start of study therapy.

Prior/Concurrent Clinical Study Experience:
3. Administration of an IP (eg, drug or vaccine) concurrent with study intervention or within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). A participant may be eligible if they are in the follow-up phase of an investigational study if
they meet the criterion for time elapsed from previous administration of IP. Cases must be discussed with sponsor's medical monitor to judge eligibility.
Diagnostic Assessments:
4. Serum or urine pregnancy test positive at screening.
5.

Critères d'évaluation principaux et secondaires
Main Objective: To demonstrate the superiority of Inotuzumab Ozogamicin (InO) monotherapy vs ALLR3 induction in paediatric participants between 1 and less than 18 years with HR first bone marrow relapse CD22-positive B-cell precursor acute lymphoblastic leukaemia (BCP ALL.);Secondary Objective: To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to event-free survival (EFS).
To evaluate the long-term efficacy of InO monotherapy vs ALLR3 regimen with respect to:
? Duration of response (DOR)
? Hematopoietic stem cell transplant (HSCT) rate
? Chimeric antigen receptor (CAR) T-cell therapy
? Overall survival (OS)
To evaluate the safety and tolerability of InO monotherapy vs ALLR3 induction
To evaluate the pharmacokinetics (PK) of InO
;Primary end point(s): Minimal residual disease (MRD)-negative, CR/CRp/CRi (per investigator assessment) at the end of induction therapy (MRD negativity is assessed by central lab and defined as leukemic blasts <1x10-4 by real time quantitative polymerase chain reaction (RQ-PCR) [with reflex to FC result if MRD is non-evaluable by RQ-PCR]). ;Timepoint(s) of evaluation of this end point: MRD-negative, CR/CRp/CRi (per investigator assessment) will be evaluated at the end of induction therapy (ICTRP)

Secondary end point(s): EFS, defined as the time from randomization until objective progression, relapse from CR/CRp/CRi, based on investigator assessment per response criteria, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT, second malignancy, or death due to any cause.

DOR, defined as time from date of first documented response (CR/CRp/CRi) to the date of first documented objective progression, relapse from CR/CRp/CRi as determined by investigator assessment per modified NCCN response criteria, MRD persistence prior to HSCT, or death due to any cause, whichever occurs first.

HSCT (and CAR T-cell therapy) rate, defined as the number and percentage of participants being transplanted and those receiving CAR T-cell therapy after treatment with InO or ALLR3.

OS, defined as the time from the date of randomization to the date of death due to any cause.

Incidence and severity of AEs graded per NCI CTCAE v4.03.

Cmax and Ctrough

;Timepoint(s) of evaluation of this end point: EFS will be evaluated from randomization until objective progression, relapse from CR/CRp/CRi, based on investigator assessment per response criteria, failure to achieve CR/CRp/CRi by the end of induction, MRD persistence prior to HSCT, second malignancy, or death due to any cause.


(ICTRP)

Date d'enregistrement
08.11.2022 (ICTRP)

Inclusion du premier participant
21.02.2023 (ICTRP)

Sponsors secondaires
non disponible

Contacts supplémentaires
Clinical Trials.gov Call Centre, ClinicalTrials.gov_Inquiries@pfizer.com, +1800718-1021, Pfizer Inc. (ICTRP)

ID secondaires
B1931036, 2022-000186-40-HU (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2022-000186-40 (ICTRP)