Clinical trial • Phase III • Oncology

IMATINIB for Acute lymphoblastic leukemia | Philadelphia chromosome-positive acute lymphoblastic leukemia

Phase III trial of IMATINIB for Acute lymphoblastic leukemia | Philadelphia chromosome-positive acute lymphoblastic leukemia.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Acute lymphoblastic leukemia | Philadelphia chromosome-positive acute lymphoblastic leukemia
Trial Stage
Phase III
Drug Modality
Small molecule|Peptide/protein/enzyme
Paediatric Trial
Yes

Key dates

Initial CTIS Submission Date
18-09-2024
First CTIS Authorization Date
25-10-2024

Trial design

Randomised, imatinib combined with the esphall chemotherapy backbone versus imatinib combined with the cog high-risk (hr) all chemotherapy backbone-controlled Phase III trial in Austria, Belgium, Czechia and others.

Randomised
Yes
Comparator
Imatinib combined with the EsPhALL chemotherapy backbone versus imatinib combined with the COG high-risk (HR) ALL chemotherapy backbone
Target Sample Size
306

Eligibility

Recruits 306 paediatric patients.

Pregnancy Exclusion
5. Pregnancy
Vulnerable Population
The trial includes vulnerable populations (minors). Age-specific subject information sheets and informed consent/assent forms are provided (documents for parents/legal guardians and for children/adolescents across age bands such as under 8, 8-11, 12-17, 15-17 and adults). Consent is obtained from the parent/legal guardian for minors with age-appropriate assent from children/adolescents where applicable; adult participants provide their own informed consent. Multiple country-specific ICFs/translations are available.

Inclusion criteria

  • {"criterion_text":"- 1. Patients should be enrolled on National ALL protocol prior to enrollment on EsPhALL2017/COGAALL1631. Regardless of initial frontline protocol baseline diagnostic samples must be available to develop an MRD probe. Diagnostic samples will be collected and analyzed according to the procedures of the National front-line protocol."}
  • {"criterion_text":"- 2. > 1 year and < 21 years at ALL diagnosis"}
  • {"criterion_text":"- 3. New LLA diagnosis a. type B or T, or mixed phenotypic acute leukemia (MPAL meeting 2016 WHO definition) with definitive evidence of BCR-ABL1 fusion by karyotype, FISH and/or RT-PCR b. type B, with definitive evidence of ABL class fusions identified according to National/Center procedures of each participating country."}
  • {"criterion_text":"- 4. Prior Therapy for BCR-ABL1 fusion patients: a. induction therapy, which includes vincristine, a corticosteroid, usually PEG-L-Asparaginase, with or without anthracycline, and/or other standard cytotoxic chemotherapy. b. Not received more than 14 days of multiagent induction therapy beginning with the first dose of vincristine. c. May have started imatinib prior to study entry but have not received more than 14 days of imatinib."}
  • {"criterion_text":"- 5. Prior Therapy for ABL-class fusion patients: a. must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy. b. may have started imatinib during Induction IA, at the same time of or after the first vincristine dose."}
  • {"criterion_text":"- 6. Patients must have a performance status corresponding to ECOG scores of 0, 1, or 2."}
  • {"criterion_text":"- 7. Adequate liver function."}
  • {"criterion_text":"- 8. Adequate cardiac function."}
  • {"criterion_text":"- 9. Adequate renal function."}

Exclusion criteria

  • {"criterion_text":"- 1. Known history of chronic myelogenous leukemia (CML)."}
  • {"criterion_text":"- 2. ALL developing after a previous cancer treated with cytotoxic chemotherapy."}
  • {"criterion_text":"- 3. Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation"}
  • {"criterion_text":"- 4. Down syndrome"}
  • {"criterion_text":"- 5. Pregnancy"}
  • {"criterion_text":"- 6. Breast Feeding"}
  • {"criterion_text":"- 7. Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of treatment according to protocol."}
  • {"criterion_text":"- 8. Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block."}
  • {"criterion_text":"- 9. Prior treatment with dasatinib, or any TKI inhibitor other than imatinib."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The primary endpoint, DFS, is defined as the time from randomization to first event (relapse, second malignancy, or death in complete remission) or time to last followup for patients without events","definition_or_measurement_approach":"Defined as the time from randomization to first event (relapse, second malignancy, or death in complete remission) or time to last followup for patients without events."}

Recruitment

Registry Or Advocacy Recruitment
True, European Hematology Association | Pohjois-Savon hyvinvointialue
Planned Sample Size
306
Recruitment Window Months
112
Consent Approach
Informed consent is obtained using age-appropriate subject information sheets and consent/assent forms. Parental/legal guardian consent is required for minors; assent forms and information sheets are provided for children/adolescents (separate documents for age bands such as under 8, 8-11, 12-17, 15-17). Adult participants provide their own consent. Multiple country-specific and language-specific ICFs are available (examples in English, French, Dutch, Italian, German, Spanish, Czech, Finnish, Swedish among others).

Geography

Total Number Of Participants
306

Austria

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
29-10-2024
Processing Time Days
18
Number Of Participants
6

Belgium

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
14
Number Of Participants
6

Czechia

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
30-10-2024
Processing Time Days
19
Number Of Participants
18

Denmark

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
27-10-2024
Processing Time Days
16
Number Of Participants
6

Finland

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
28-10-2024
Processing Time Days
17
Number Of Participants
6

France

Earliest CTIS Part Ii Submission Date
29-10-2024
Latest Decision Or Authorization Date
12-11-2024
Processing Time Days
14
Number Of Participants
66

Germany

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
14
Number Of Participants
72

Italy

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
05-11-2024
Processing Time Days
25
Number Of Participants
48

Spain

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
14
Number Of Participants
24

Sweden

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
14
Number Of Participants
12

Netherlands

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
25-10-2024
Processing Time Days
14
Number Of Participants
18

Poland

Earliest CTIS Part Ii Submission Date
11-10-2024
Latest Decision Or Authorization Date
28-10-2024
Processing Time Days
17
Number Of Participants
24

Sponsor

Primary sponsor

Full Name
Universita Degli Studi Di Milano Bicocca
Organisation Type
Educational Institution
Country Of Registered Address
Italy

Third parties

  • {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code 1","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
IMATINIB
Active Substance
IMATINIB
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Maximum Dose
800 mg
Investigational Product Name
TIOGUANINE
Active Substance
TIOGUANINE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Maximum Dose
60 mg/m2
Investigational Product Name
DOXORUBICIN HYDROCHLORIDE
Active Substance
DOXORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INJECTION
Route
INJECTION
Maximum Dose
25 mg/m2
Investigational Product Name
PEGASPARGASE
Active Substance
PEGASPARGASE
Modality
Peptide/protein/enzyme
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
2500 m2
Investigational Product Name
CYTARABINE
Active Substance
CYTARABINE
Modality
Small molecule
Routes Of Administration
INTRATHECAL USE / INJECTION / SUSPENSION FOR INJECTION
Route
INTRATHECAL/INJECTION
Maximum Dose
4000 mg/m2
Investigational Product Name
DEXAMETHASONE
Active Substance
DEXAMETHASONE
Modality
Small molecule
Routes Of Administration
ORAL AND IV
Route
ORAL AND IV
Maximum Dose
20 mg/m2
Investigational Product Name
DELTACORTENE 25 mg compresse (PREDNISONE)
Active Substance
PREDNISONE
Modality
Small molecule
Routes Of Administration
ORAL AND IV
Route
ORAL AND IV
Authorisation Status
010089035
Maximum Dose
60 mg/m2
Investigational Product Name
MERCAPTOPURINE
Active Substance
MERCAPTOPURINE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
ORAL USE
Maximum Dose
75 mg/m2
Investigational Product Name
Erwinase 10 000 U (CRISANTASPASE)
Active Substance
CRISANTASPASE
Modality
Peptide/protein/enzyme
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Authorisation Status
050520016
Maximum Dose
40000 IU
Investigational Product Name
DAUNORUBICIN HYDROCHLORIDE
Active Substance
DAUNORUBICIN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INJECTION
Route
INJECTION
Maximum Dose
30 mg/m2
Investigational Product Name
IFOSFAMIDE
Active Substance
IFOSFAMIDE
Modality
Small molecule
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
1600 mg/m2
Investigational Product Name
METHOTREXATE
Active Substance
METHOTREXATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS, INTRA-ARTERIAL, INTRATHECAL, ORAL, INFUSION (varies by formulation)
Route
IV/IT/ORAL/INFUSION
Maximum Dose
5000 mg or mg/m2 (formulation-dependent)
Investigational Product Name
CYCLOPHOSPHAMIDE
Active Substance
CYCLOPHOSPHAMIDE
Modality
Small molecule
Routes Of Administration
INJECTION
Route
INJECTION
Maximum Dose
1 mg/m2
Investigational Product Name
ETOPOSIDE
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
INFUSION
Route
INFUSION
Maximum Dose
200 mg/m2
Investigational Product Name
Vincristina Teva Italia (VINCRISTINE SULFATE)
Active Substance
VINCRISTINE SULFATE
Modality
Small molecule
Routes Of Administration
INJECTION
Route
INJECTION
Authorisation Status
038549010
Maximum Dose
2 mg
Investigational Product Name
HYDROCORTISONE SODIUM SUCCINATE
Active Substance
HYDROCORTISONE SODIUM SUCCINATE
Modality
Small molecule
Routes Of Administration
INTRATHECAL USE / INJECTION/INFUSION
Route
INTRATHECAL/INJECTION/INFUSION
Maximum Dose
12 mg
Combination Treatment
Yes

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