ALLIC 2022 international clinical investigation for advanced management of childhood acute lymphoblastic leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Semmelweis University

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Decision date (initial)

2025-01-13

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Therapy, Efficacy, Pharmacogenomic

The objectives for the ALLIC-BFM 2022 Protocol are directed to improve survival rates, to reduce morbidity and mortality and to answer randomized questions, in order to find new strategies for achieving a more accurate treatment for children with ALL. The aims will be the following:
1. To improve the EFS probability of children with ALL.
2. To achieve a better risk group definition:
2.1. Improving genetic studies at diagnosis.
2.2. Adding MRD determinations on day 33 and day 78 by Flow-Cytometry (FC).
3. To decrease deaths during induction phase rate and deaths in Complete Remission rate.
4. To evaluate the role of intensified treatment element with PEG-asparaginase (Peg-Asp).
5. To evaluate the impact of immunotherapy (anti CD20) for Bcp-ALL patients.

Secondary objectives 5

1. 1. To improve the EFS probability of children with ALL.
2. 2. To achieve a better risk group definition: 2.1. Improving genetic studies at diagnosis. 2.2. Adding MRD determinations on day 33 and day 78 by Flow-Cytometry.
3. 3. To decrease deaths during induction phase rate and deaths in Complete Remission rate.
4. 4. To evaluate the role of intensified treatment element with PEG-asparaginase.
5. 5. To evaluate the impact of immunotherapy (anti CD20) for Bcp-ALL patients.

Conditions and MedDRA coding

Childhood non-mature-B Acute Lymphoblastic Leukemia

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

National Center For Public Health And Pharmacy

EMA paediatric investigation plan (PIP)

EMEA-000341-PIP03-18

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age at diagnosis 1- <18 years.
2. 2. Start of induction therapy within the enrollment period of the trial: from December 1st, 2022 through December 31, 2028.
3. 3- Diagnosis of ALL ensured by all the diagnostic criteria defined in the protocol.
4. 4.Informed consent to participate in ALL IC-BFM 2022 trial available.
5. 5. Admission, diagnosis, and therapy performed by a center participating in the study.
6. 6. Urine βHCG is negative in female patient with childbearing potential.

Exclusion criteria 3

1. Positive HBV serology (hepatitis B surface (HBs) antigen positive and HBc antibody positive/HBs antibody negative) and TBC documentation.
2. Pregnant or breastfeeding patient
3. Known allergy or contraindication (based on SmPC) to both IMPs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be the minimum time from the randomization until the first event: non-response after HR2 consolidation block, relapse, second malignancy or death from any cause (EFS time).

Secondary endpoints 5

1. Time to death from any cause, measured from the time of randomization (survival time).
2. End of induction (day 33) and end of early intensification (day 78) MRD status.
3. Safety of rituximab in combination with intensive chemotherapy: -Death in CR will be compared between the two arms. -The rate of severe infections (CTC grade 3 to 5) during the treatment and until the end of chemotherapy will be compared between the two arms. -The rate of rituximab infusion reactions (total number and by severity of reactions) will be estimated. -The rate of intensive care unit admissions will be compared between the two arms.
4. -Occurrence of infections on the target list (presumably associated with rituximab) will be compared between the two arms: cytomegalovirus, progressive multifocal leukoencephalopathy and Herpes zoster. -Need for immunoglobulin substitution will be compared between the two arms. IgG level will be measured at day 0 and then by physician discretion, but at least once monthly until the end of intensive chemotherapy and once every 3 months during maintenance chemotherapy until reaching normal level w
5. Additional Researchs: -To determine the relationship between CD20 expression on ALL blasts (initially, day 15, day 33, day 78) and response to monoclonal antibody therapy. -To determine whether the administration of an anti-B cell monoclonal antibody limits the incidence of peg-asparaginase allergy occurrence.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Semmelweis University

Sponsor organisation

Semmelweis University

Address

Tuzolto Utca 7-9

City

Budapest

Postcode

1094

Country

Hungary

Scientific contact point

Organisation

Semmelweis University

Contact name

Gabor Dr. Kovács

Public contact point

Organisation

Semmelweis University

Contact name

Gabor Dr. Kovács

Third parties 4

Locations

4 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications