Study on chemotherapy and experimental drugs in patients with Philadelphia Chromosome positive and ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita Degli Studi Di Milano Bicocca

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

9 Dec 2025 → ongoing

Decision date (initial)

2025-12-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

1. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults with newly-diagnosed Ph+ (BCR::ABL1-rearranged) B-ALL who are treated with a modified Berlin-Frankfurt-Münster (mBFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib.
2. To estimate the 3-year EFS of children, adolescents, and young adults with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without PDGFRB gene fusions
3. To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays > 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous TKI.

Secondary objectives 4

1. To estimate the 3-year overall survival (OS) of patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
2. To estimate the 3-year EFS, disease-free survival (DFS), cumulative incidence rates (CIR) of relapse, and treatment related mortality (TRM), and OS of patients with ABL-class Ph-like B-ALL stratified by their underlying ABL-class fusion subtypes.
3. To describe rates of end of Consolidation (EOC)/timepoint 2 (TP2) minimal residual disease (MRD) negativity defined as <1x10-4 or <0.01% for patients with Ph+ B-ALL.
4. To describe rates of EOC/TP2 MRD negativity defined as <1x10-4 or <0.01% for patients with ABL-class Ph-like B-ALL collectively and based on their ABL-class fusion subtypes.

Conditions and MedDRA coding

Philadelphia Chromosome Positive or ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patients must be >365 days and <18 years (for AIEOP-BFM), >365 days and <22 years (for COG) and >365 days and <46 years (for ALLTogether sites) at the time of enrollment.
2. Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB.
3. Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on Day 15 from the first dose of vincristine during Induction therapy.
4. Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy.
5. Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vincristine.
6. Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy
7. Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL.
8. Patients must have a performance status corresponding to ECOG scores of ≤2 or Karnofsky and Lansky performance scores ≥50%. Use Karnofsky for patients >16 years of age and Lansky for patients ≤ 16 years of age.
9. Adequate renal function
10. Adequate liver function
11. Adequate cardiac function

Exclusion criteria 11

1. Known history of chronic myeloid leukemia (CML)
2. ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase.
3. 3. ALL developing after a previous cancer treated with cytotoxic chemotherapy
4. Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
5. Down syndrome (trisomy 21)
6. Pregnancy and breast feeding
7. Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
8. Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
9. Patients with known Charcot-Marie-Tooth disease
10. Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement
11. HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults <25 years old with newly-diagnosed Ph+ B-ALL who are treated with a modified Berlin-Frankfurt-Münster (BFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib
2. To estimate the 3-year EFS of children, adolescents, and young adults <25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB fusions or dasatinib for those without PDGFRB fusions
3. To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays > 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous TKI.

Secondary endpoints 3

1. To estimate the 3-year overall survival (OS) of patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
2. To estimate the 3-year EFS, disease-free survival (DFS), cumulative incidence rates (CIR) of relapse, and treatment related mortality (TRM), and OS of patients with ABL-class Ph-like B-ALL stratified by their underlying ABL-class fusion subtypes
3. To describe rates of EOC/TP2 MRD negativity defined as <1x10-4 or <0.01% for patients with ABL-class Ph-like B-ALL collectively and based on their ABL-class fusion subtypes.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita Degli Studi Di Milano Bicocca

Sponsor organisation

Universita Degli Studi Di Milano Bicocca

Address

Piazza Dell'ateneo Nuovo 1

City

Milan

Postcode

20126

Country

Italy

Scientific contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Adriana Balduzzi

Public contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Adriana Balduzzi

Third parties 1

Locations

13 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 95 files

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

Application history

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