AIEOP-BFM 2017 POLAND - Collaborative treatment protocol for children and adolescents with acute lymphoblastic leukemia - A randomized phase III study conducted in agreement with the AIEOP-BFM study group

2024-517253-27-00 Protocol AIEOP-BFM 2017POLAND Therapeutic confirmatory (Phase III) Ongoing, recruitment ended

Start 1 Jul 2021 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 15 sites · Protocol AIEOP-BFM 2017POLAND

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ongoing, recruitment ended
Participants planned 874
Countries 1
Sites 15

Acute lymphoblastic leukemia

(1a) Randomization R-eHR: In children with early high-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the pEFS from time of randomization be improved by additional therapy with the proteasome inhibitor Bortezomib during an extended consolidation treatmen…

Key facts

Sponsor
Medical University Of Silesia Katowice Poland
Participant type
Pediatric, Patients
Age range
0-17 years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
1 Jul 2021 → ongoing
Decision date (initial)
2024-10-28
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Polish Medical Research Agency

External identifiers

EU CT number
2024-517253-27-00
EudraCT number
2020-005017-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

(1a) Randomization R-eHR: In children with early high-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the pEFS from time of randomization be improved by additional therapy with the proteasome inhibitor Bortezomib during an extended consolidation treatment phase compared with standard extended consolidation?
(2a) Randomization R-HR: In children with high-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the immunotherapy with Blinatumomab (three cycles, 15 μg/m²/d for 28 days per cycle) plus 6 doses intrathecal Methotrexate decrease the frequency of life-threatening treatment-related toxicities without decreasing the frequency of achieving negative MRD compared with standard post-consolidation chemotherapy (HR blocks) regimen?

Secondary objectives 8

  1. (1b) eHR randomization: Can the overall survival be improved by the treatment in the experimental arm.
  2. (1c) eHR randomization: What is the incidence of treatment-related toxicities and mortality in the experimental arm compared to the standard arm.
  3. (1d) eHR randomization: Can the MRD load after consolidation treatment be reduced by the additional treatment with Bortezomib?
  4. (2b) R-HR: What is the change of MRD load associated with treatment with blinatumomab compared with standard HR blocks?
  5. (2c) R-HR: What are the dynamics of MRD load in children treated with blinatumomab at predefined timepoints compared with those receiving standard high-intensity post-consolidation therapy?
  6. (2d) R-HR: What is the proportion of patients with poor response to Blinatumomab as defined in the protocol as compared to the MRD response after the HR-1’ and HR-2’ block in the control arm?
  7. (2e) R-HR: What are the clinical outcomes (frequency of MRD-negativity, pEFS, pOS) in patients randomized to blinatumomab compared with those those randomized to standard HR-blocks joined with historic patients receiving HR-blocks according to the same protocol.
  8. (1e, 2f) R-eHR, R-HR: What are the clinical outcomes of patients treated in experimental arms compared to those treated in control arms of the original AIEOP-BFM ALL 2017 study?

Conditions and MedDRA coding

Acute lymphoblastic leukemia

VersionLevelCodeTermSystem organ class
21.0 LLT 10000845 Acute lymphoblastic leukemia 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. newly diagnosed acute lymphoblastic leukemia or
  2. newly diagnosed acute undifferentiated leukemia or
  3. newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following criteria: • biphenotypic with a dominant T or B lineage assignment • bilineal either with a dominant lymphoblastic population or if another reasonable rationale exists to treat the patient with an ALL-based therapy regimen
  4. age < 18 years (up to 17 years and 365 days) at the day of diagnosis
  5. patient enrolled in a participating center
  6. written informed consent to trial participation and transfer and processing of data

Exclusion criteria 12

  1. Ph+ (BCR::ABL1 or t(9;22)-positive) ALL
  2. bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (≥ 10% of total cells) blast subset
  3. pre-treatment with cytostatic drugs
  4. glucocorticoid pre-treatment with ≥ 1 mg/kg/d Prednisolone equivalent for more than two weeks during the last month before diagnosis
  5. treatment started according to another protocol
  6. underlying disease that does not allow treatment according to the protocol
  7. ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
  8. evidence of pregnancy or lactation period
  9. Sexually active adolescents not willing to use highly effective contraceptive method (Pearl Index <1) until 12 months after end of anti-leukemic therapy
  10. participation in another clinical trial except for ad-on trials within the scope of supportive care approved by the sponsor
  11. other condition (either pre-existing or related to leukemia biology as present at diagnosis) or circumstances that significantly conflict with the treatment according to the protocol
  12. live vaccine immunization within 2 weeks before start of protocol treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. R-eHR: The primary endpoint will be the time from randomization until the first event defined as follows: • Cytomorphological or molecular non-response (resistance to protocol treatment, considered as event after post-consolidation treatment – HR blocks or blinatumomab therapy), • relapse, • second malignancy or death from any cause. This will be called EFS time.
  2. (2a) R-HR: Frequency and incidence of grade 4 adverse events or death from any cause, non-serious adverse events of medical interest during post-consolidation treatment (blinatumomab and HR blocks)
  3. (2a) R-HR: Frequency of MRD-negative patients after first and third cycle of Blinatumomab or after the HR-1’/HR-3’ block compared under non-inferiority assumption

Secondary endpoints 9

  1. (1b) Time from randomization to death from any cause
  2. (1c) Frequency and incidence of grade 4 adverse events or death during Consol Bext and after but before 1st day of HR-1` block or 1st blinatumomab cycle.
  3. (1c, 2a) Frequency and incidence of AE of special interest and SAE in specific protocol phases, randomized arms and overall during follow-up
  4. (1d) Proportion of children with negative MRD at TP1a and TP2
  5. (2b) Absolute difference in MRD load between TP2 and TP after first blinatumomab cycle or HR-1
  6. (2b) Absolute difference in MRD load between TP2 and third Blinatumomab cycle or HR-3`
  7. (2c) Absolute MRD loads at TP2 and TP HR Blina 1, d29 71, 113 and TP2, TP HR1, TP HR2, TP HR3.
  8. (2d) Time from the first day of first Blinatumomab cycle or HR-1` block to event: death from any cause (for OS), death, relapse, secondary malignancy or molecular non-response for EFS).
  9. (1e, 2f) R-eHR, R-HR: appropriately-defined times to events, frequencies of grade 4 adverse events or death and proportion of patients achieving negative MRD at corresponding timepoints.

Investigational products

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

Test 42

Ifosfamide

SUB08125MIG · Substance

Active substance
Ifosfamide
Pharmaceutical form
POWDER FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
800 mg/m2 milligram(s)/sq. meter
Max total dose
4000 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Ifosfamide

SUB08125MIG · Substance

Active substance
Ifosfamide
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
800 mg/m2 milligram(s)/sq. meter
Max total dose
4000 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dexamethasone

SUB07017MIG · Substance

Active substance
Dexamethasone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
1040 mg/m2 milligram(s)/sq. meter
Max treatment duration
115 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dexamethasone

SUB07017MIG · Substance

Active substance
Dexamethasone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
1040 mg/m2 milligram(s)/sq. meter
Max treatment duration
115 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Blinatumomab

SUB35403 · Substance

Active substance
Blinatumomab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
15 µg/ m2 microgram(s)/ sq. Meter
Max total dose
1260 µg/ m2 microgram(s)/ sq. Meter
Max treatment duration
84 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Fludarabine Phosphate

SUB13897MIG · Substance

Active substance
Fludarabine Phosphate
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
150 mg/m2 milligram(s)/square meter
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tioguanine

SUB11084MIG · Substance

Active substance
Tioguanine
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
2520 mg/m2 milligram(s)/sq. meter
Max treatment duration
42 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone

SUB10018MIG · Substance

Active substance
Prednisolone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone Sodium Succinate

SUB04019MIG · Substance

Active substance
Prednisolone Sodium Succinate
Pharmaceutical form
POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone Sodium Succinate

SUB04019MIG · Substance

Active substance
Prednisolone Sodium Succinate
Pharmaceutical form
POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone Sodium Succinate

SUB04019MIG · Substance

Active substance
Prednisolone Sodium Succinate
Pharmaceutical form
POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisolone Sodium Succinate

SUB04019MIG · Substance

Active substance
Prednisolone Sodium Succinate
Pharmaceutical form
POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Crisantaspase

SUB33789 · Substance

Active substance
Crisantaspase
Pharmaceutical form
POWDER FOR SOLUTION/SUSPENSION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
20000 IU international unit(s)
Max total dose
1260000 IU international unit(s)
Max treatment duration
63 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Bortezomib

SUB20020 · Substance

Active substance
Bortezomib
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1.3 mg/m2 milligram(s)/sq. meter
Max total dose
5.2 mg/m2 milligram(s)/sq. meter
Max treatment duration
4 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Pegaspargase

SUB03666MIG · Substance

Active substance
Pegaspargase
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
3750 IU international unit(s)
Max total dose
33750 IU international unit(s)
Max treatment duration
9 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Etoposide

SUB07337MIG · Substance

Active substance
Etoposide
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 mg/m2 milligram(s)/square meter
Max total dose
500 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Etoposide

SUB07337MIG · Substance

Active substance
Etoposide
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 mg/m2 milligram(s)/sq. meter
Max total dose
500 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Etoposide

SUB07337MIG · Substance

Active substance
Etoposide
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 mg/m2 milligram(s)/sq. meter
Max total dose
500 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Etoposide

SUB07337MIG · Substance

Active substance
Etoposide
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 mg/m2 milligram(s)/sq. meter
Max total dose
500 mg/m2 milligram(s)/sq. meter
Max treatment duration
3 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Doxorubicin Hydrochloride

SUB01827MIG · Substance

Active substance
Doxorubicin Hydrochloride
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
180 mg/m2 milligram(s)/sq. meter
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Doxorubicin Hydrochloride

SUB01827MIG · Substance

Active substance
Doxorubicin Hydrochloride
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
180 mg/m2 milligram(s)/sq. meter
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Doxorubicin Hydrochloride

SUB01827MIG · Substance

Active substance
Doxorubicin Hydrochloride
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
180 mg/m2 milligram(s)/sq. meter
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Doxorubicin Hydrochloride

SUB01827MIG · Substance

Active substance
Doxorubicin Hydrochloride
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
180 mg/m2 milligram(s)/sq. meter
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Mercaptopurine

SUB12149MIG · Substance

Active substance
Mercaptopurine
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
50 mg/m2 milligram(s)/sq. meter
Max total dose
31080 mg/m2 milligram(s)/sq. meter
Max treatment duration
644 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cyclophosphamide

SUB06859MIG · Substance

Active substance
Cyclophosphamide
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
1000 mg/m2 milligram(s)/sq. meter
Max total dose
5500 mg/m2 milligram(s)/sq. meter
Max treatment duration
9 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cytarabine

SUB06880MIG · Substance

Active substance
Cytarabine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
2000 mg/m2 milligram(s)/sq. meter
Max total dose
15000 mg/m2 milligram(s)/sq. meter
Max treatment duration
43 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cytarabine

SUB06880MIG · Substance

Active substance
Cytarabine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
2000 mg/m2 milligram(s)/sq. meter
Max total dose
15000 mg/m2 milligram(s)/sq. meter
Max treatment duration
43 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cytarabine

SUB06880MIG · Substance

Active substance
Cytarabine
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
2000 mg/m2 milligram(s)/sq. meter
Max total dose
15000 mg/m2 milligram(s)/sq. meter
Max treatment duration
43 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexate Disodium

SUB16442MIG · Substance

Active substance
Methotrexate Disodium
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRATHECAL USE
Max daily dose
12 mg milligram(s)
Max total dose
312 mg milligram(s)
Max treatment duration
26 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexate

SUB08856MIG · Substance

Active substance
Methotrexate
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
1600 mg/m2 milligram(s)/sq. meter
Max treatment duration
80 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexate

SUB08856MIG · Substance

Active substance
Methotrexate
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
1600 mg/m2 milligram(s)/sq. meter
Max treatment duration
80 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexate

SUB08856MIG · Substance

Active substance
Methotrexate
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
1600 mg/m2 milligram(s)/sq. meter
Max treatment duration
80 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Methotrexate

SUB08856MIG · Substance

Active substance
Methotrexate
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRATHECAL USE
Max daily dose
12 mg milligram(s)
Max total dose
312 mg milligram(s)
Max treatment duration
26 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dexamethasone Phosphate

SUB01612MIG · Substance

Active substance
Dexamethasone Phosphate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
20 mg/m2 milligram(s)/sq. meter
Max total dose
115 mg/m2 milligram(s)/sq. meter
Max treatment duration
115 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Vindesine Sulfate

SUB05102MIG · Substance

Active substance
Vindesine Sulfate
Pharmaceutical form
POWDER FOR SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
3 mg/m2 milligram(s)/sq. meter
Max total dose
6 mg/m2 milligram(s)/sq. meter
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Vincristine Sulfate

SUB05101MIG · Substance

Active substance
Vincristine Sulfate
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
2 mg milligram(s)
Max total dose
28 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Daunorubicin Hydrochloride

SUB01556MIG · Substance

Active substance
Daunorubicin Hydrochloride
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
30 mg/m2 milligram(s)/sq. meter
Max total dose
150 mg/m2 milligram(s)/sq. meter
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Cytarabine

SUB06880MIG · Substance

Active substance
Cytarabine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS
Max daily dose
2000 mg/m2 milligram(s)/sq. meter
Max total dose
15000 mg/m2 milligram(s)/sq. meter
Max treatment duration
43 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisone

SUB10020MIG · Substance

Active substance
Prednisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisone

SUB10020MIG · Substance

Active substance
Prednisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisone

SUB10020MIG · Substance

Active substance
Prednisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Prednisone

SUB10020MIG · Substance

Active substance
Prednisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
60 mg/m2 milligram(s)/sq. meter
Max total dose
1837.5 mg/m2 milligram(s)/sq. meter
Max treatment duration
37 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Silesia Katowice Poland

3 Total trials 2 Recruiting 1 Ended
Academic / Non-commercial
Sponsor organisation
Medical University Of Silesia Katowice Poland
Address
Ul. Ksiecia Jozefa Poniatowskiego 15
City
Katowice
Postcode
40-055
Country
Poland

Scientific contact point

Organisation
Medical University Of Silesia Katowice Poland
Contact name
Clinical Trial Support Unit

Public contact point

Organisation
Medical University Of Silesia Katowice Poland
Contact name
Clinical Trial Support Unit

Locations

1 EU/EEA country · 15 investigational sites

By country

CountryMS statusPlanned subjectsSites
Poland Ongoing, recruitment ended 874 15
Rest of world — 0 —

Investigational sites

Poland

15 sites · Ongoing, recruitment ended
Uniwersytecki Szpital Kliniczny Nr 1 Im. Prof. Tadeusza Sokolowskiego Pum W Szczecinie
Klinika Pediatrii, Hemato-onkologii i Gastroenterologii Dziecięcej, Ul. Unii Lubelskiej 1, 71-252, Szczecin
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
Ponadregionalne Centrum Onkologii Dziecięcej "Przylądek Nadziei", Ul. Borowska 213, 50-556, Wroclaw
Szpital Uniwersytecki Nr 1 Im. Dr. A. Jurasza W Bydgoszczy
Klinika Pediatrii, Hematologii i Onkologii, Ul. Marii Curie Sklodowskiej 9, 85-094, Bydgoszcz
Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach
Oddział Onkologii i Hematologii Dziecięcej, Ul. Prezydenta Stefana Artwinskiego 3, 25-734, Kielce
Samodzielny Publiczny Dzieciecy Szpital Kliniczny Im. Jozefa Polikarpa Brudzinskiego W Warszawie
Oddział Kliniczny Pediatrii, Hematologii i Onkologii, Ul. Ulica Zwirki I Wigury 63 A, 02-091, Warsaw
Wojewodzki Specjalistyczny Szpital Dzieciecy Im. Prof. Dr Stanislawa Popowskiego W Olsztynie Sp. z o.o.
Oddział Kliniczny Onkologii i Hematologii Dziecięcej, Ul. Zolnierska 18 A, 10-561, Olsztyn
Uniwersytecki Szpital Dzieciecy W Krakowie
Klinika Onkologii i Hematologii Dziecięcej, Ul. Wielicka 265, 30-663, Cracow
Uniwersytecki Dzieciecy Szpital Kliniczny Im. L. Zamenhofa W Bialymstoku
Klinika Pediatrii, Onkologii i Hematologii, Ul. Jerzego Waszyngtona 17, 15-274, Bialystok
Uniwersyteckie Centrum Kliniczne
Klinika Pediatrii, Hematologii i Onkologii, Ul. Debinki 7, 80-211, Gdansk
Kliniczny Szpital Wojewodzki Nr 2 Im. Sw. Jadwigi Krolowej W Rzeszowie
Klinika Onkohematologii Dziecięcej, Ul. Lwowska 60, 35-301, Rzeszow
Uniwersytecki Szpital Dzieciecy W Lublinie
Klinika Hematologii, Onkologii i Transplantologii Dziecięcej, Ul. Prof. Antoniego Gebali Nr 6, 20-093, Lublin
Samodzielny Publiczny Szpital Kliniczny Nr 1 Im.Prof.Stanislawa Szyszko Slaskiego Uniwersytetu Medycznego W Katowicach
Oddział Hematologii i Onkologii Dziecięcej, Ul. 3 Maja 13/15, 41-800, Zabrze
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi
Klinika Pediatrii, Onkologii, Hematologii i Diabetologii, Ul Sporna 36/50, 91-738, Lodz
Gornoslaskie Centrum Zdrowia Dziecka Im. Sw. Jana Pawla II Samodzielny Publiczny Szpital Kliniczny Nr 6 Slaskiego Uniwersytetu Medycznego W Katowicach
Oddział Onkologii, Hematologii i Chemioterapii, Ul. Medykow 16, 40-752, Katowice
Szpital Kliniczny Im. Karola Jonschera Uniwersytetu Medycznego Im. Karola Marcinkowskiego W Poznaniu
Klinika Onkologii, Hematologii i Transplantologii Pediatrycznej, Ul. Szpitalna 27/33, 60-572, Poznan

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Poland 2021-07-01 2021-07-01 2024-11-08

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Serious breach SB-78839

Sponsor became aware
2025-04-07
Date of breach
2025-03-24
Submission date
2025-04-11
Member states concerned
Poland
Categories
Protocol
Areas impacted
Subject safety
Benefit-risk balance changed
No
Description
Modification of treatment regimen in one patient.
Sponsor actions
Treatment was corrected promptly upon deviation detection.
Root cause analysis was performed. Corrective actions, including enhanced training, process revisions and double-check system implementation are expected to prevent recurrence. Patient safety has been prioritized and no other patients were affected. The patient has not experienced immediate adverse reactions – only the occurrence of infection of unknown aetiology, which is expected at any stage of treatment, was noted. Continued monitoring is in place to identify and address any delayed effects. The occurrence of the serious breach did not require the exclusion of the participant from the study, the patient continues to participate in the study.
OrganisationCityCountryType
Wojewodzki Specjalistyczny Szpital Dzieciecy Im. Prof. Dr Stanislawa Popowskiego W Olsztynie Sp. z o.o. Olsztyn Poland Clinical investigator

Results and documents

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

Documents 33 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-517253-27-00 4.0
Recruitment arrangements (for publication) K1_Recruitment arrangements_redacted 1
Subject information and informed consent form (for publication) L1_IS parents_legal guardians and ICF 3.2
Subject information and informed consent form (for publication) L1_SIS 11-15 yr 1.1
Subject information and informed consent form (for publication) L1_SIS 16-18 yr 3.2
Subject information and informed consent form (for publication) L1_SIS under 11 yr 1.0
Subject information and informed consent form (for publication) L2_Other subject information material_ICF_Personal data processing 2.0
Subject information and informed consent form (for publication) L2_Other subject information material_Subject information card 1.0
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_BLINATUMOMAB 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_BORTEZOMIB 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CRISANTASPASE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CYCLOPHOSPHAMIDE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CYTARABINE_20 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_CYTARABINE_50 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_DAUNURUBICINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_DEXAMETHASONE_IV 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_DEXAMETHASONE_PO 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_DOXORUBICINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_ETOPOSIDE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_FLUDARABINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_IFOSFAMIDE_1 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_IFOSFAMIDE_2 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_MERCAPTOPURINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_METHOTREXATE_10_IV 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_METHOTREXATE_100_IV 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_METHOTREXATE_PO 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_PEGASPARAGINASE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_PREDNISONE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_PREDNISONOLE_IV 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_PREDNISONOLE_PO 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_THIOGUANINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_VINCRISTINE 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC_VINDESINE 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-08-28 Poland Acceptable
2024-10-21
 2024-10-28

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