This study has been transitioned to CTIS with ID 2024-515499-12-00 check the CTIS register for the current data. The primary objective is reducing treatment-related morbidity and mortality without adversely impacting DFS in Ph+ ALL patients,…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To compare disease-free survival (DFS) of Standard Risk (SR) pediatric Ph+ ALL
treated with continuous imatinib combined with either a high-risk
COG ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy
backbone.
Secondary outcome
- To compare disease free survival (DFS) of SR pediatric Ph+ and ABL-class
fusion positive ALL patients treated with continuous imatinib combined with
either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL
chemotherapy backbone.
- To determine the feasibility of administration of imatinib after allogeneic
HSCT in High Risk (HR) Ph+ ALL patients.
- To determine event-free-survival (EFS) of HR pediatric Ph+ ALL patients
treated with EsPhALL chemotherapy, HSCT in first complete remission and
post-HSCT imatinib.
- To compare rates of Grade 3 or higher infections in SR Ph+ ALL patients
between the two randomized arms.
- To evaluate EFS and overall survival (OS) of all eligible Ph+ALL patients
enrolled on the study.
- To evaluate OS in SR Ph+ ALL patients.
- To evaluate OS in HR Ph+ ALL patients.
- To evaluate EFS and OS of all eligible ABL-class fusion positive ALL patients
enrolled on the study.
Background summary
Approximately 3-5% of pediatric ALL patients present with the Philadelphia
chromosome (Ph+ ALL). Historically, patients with Ph+ ALL had a poor prognosis
and were considered candidates for allogeneic hematopoietic stem cell
transplant (HSCT) in first complete remission (CR1). Studies conducted by COG
and the European EsPhALL consortium over the last decade have demonstrated that
the majority of pediatric Ph+ ALL patients are effectively treated with the
combination of a tyrosine kinase inhibitor (TKI) and chemotherapy, without HSCT
in CR1. However, the cytotoxic chemotherapy backbone administered in these
trials was more intensive than is standardly used in COG for non-Ph+ pediatric
B-ALL, resulting in high rates of treatment-related toxicities (including
life-threatening infections) and mortality, as well as increased risk of late
effects.
ABL-class fusion positive B-ALL subtypes other than BCR-ABL1 have a biological
profile similar to Ph+ ALL. These patients have an overall poor prognosis, with
most patients treated with high risk chemotherapy and extensive use of HSCT in
CR1 which was associated with a high treatment-related mortality. These
patients show favourable response to TKI. This suggests that patients with
ABL-class fusion positive ALL may benefit from the treatment strategy adopted
for Ph+ ALL.
Reduction in treatment-related toxicities, if achievable without compromising
disease-free survival (DFS), would represent an important advance for this
patient population. EsPhALL 2017/COG AALL1631 is an international collaborative
protocol conducted by COG and EsPhALL.
Study objective
This study has been transitioned to CTIS with ID 2024-515499-12-00 check the CTIS register for the current data.
The primary objective is reducing treatment-related morbidity and mortality
without adversely impacting DFS in Ph+ ALL patients, classified as Standard
Risk (SR) based on low minimal residual disease (MRD) at week 10-12 of therapy.
Because there is variability in clinical practice regarding the use of TKI*s
post-HSCT in Ph+ ALL, the feasibility and outcome of post-HSCT imatinib
administration in HR pediatric Ph+ ALL patients will be tested.
Study design
Ph+ ALL patients will enter the trial at Day 15 of Induction IA and begin daily
imatinib at that time. After the Induction IB phase (week 10-12), MRD
will be assessed by immunoglubulin-T-cell-receptor (IgH-TCR) PCR, and patients
will be classified as SR (those with MRD < 5 x 10-4) or High Risk (HR; MRD > 5
x 10-4).
SR patients will be randomized to receive one of two cytotoxic chemotherapy
backbones: 1) the EsPhALL backbone (Arm A) used in previous EsPhALL protocols
and COG AALL1122/CA180372 or 2) a less intensive regimen similar to those
typically administered to non-Ph+ ALL HR patients on COG trials (Arm B).
Patients on both arms will continue to receive imatinib until the completion of
all planned chemotherapy (two years of
treatment).
For HR patients (approximately 15-20% of patients), allogeneic HSCT in CR1 is
still considered the treatment of choice. HR patients will receive the EsPhALL
chemotherapy backbone and proceed to HSCT after completion of the three
consolidation blocks.
Intervention
SR patients: imatinib combined with 1) EsPhALL chemotherapy scheme or 2) HR
COG-ALL chemotherapy scheme
HR patients: standard imatinib combined with chemotherapy pre-SCT and imatinib
post-SCT (standard, no intervention)
Study burden and risks
The treatment in Induction, the standardarm for SR patients, and the treatment
of HR patients is considered as best available treatment by the DCOG. There is
no increased risk or burden compared to the standard treatment with
chemotherapy. In the experimental arm form SR patients a less intensive
chemotherapy regimen is given, which may result in less treatment-related
toxicity, but also in an increased risk of relapse.
Imatinib is standard treatment for children with Ph+ ALL and is also standard
administered post-SCT in HR patients.
Piazza dellAteneo Nuovo 1
Milaan 20126
IT
Piazza dellAteneo Nuovo 1
Milaan 20126
IT
Listed location countries
Age
Inclusion criteria
1. Enrollment on National ALL protocol prior to enrollment on
EsPhALL2017/COGAALL1631.
2. Age >1 year and <21 years at ALL diagnosis.
3. Newly diagnosed ALL :
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 (in The
Netherlands these patients are treated according to another protocol, and will
therefore not be included in the EsPhALL2017/COGAALL1631 trial)
4. Prior therapy for BCR-ABL1 fusion patients:
- Induction therapy which includes vincristine, a corticosteroid,
usually PEG-L-Asparaginase, with or without anthracycline, and/or other
standard cytotoxic chemotherapy.
- Not received more than 14 days of multiagent Induction therapy
beginning with the first dose of vincristine.
- May have started imatinib prior to study entry but have not received
more than 14 days of imatinib.
5. Prior therapy for ABL-class patients:
- Must have previously completed the 4 or 5 weeks of multiagent
Induction chemotherapy
- May have started imatinib during Induction IA, at the same time of or
after the first vincristine dose.
6. Performance status corresponding to ECOG scores of 0, 1, or 2.
7. Adequate liver function.
8. Adequate cardiac function.
9. Adequate renal function.
Exclusion criteria
1. Known history of chronic myelogenous leukemia (CML).
2. ALL developing after a previous cancer treated with cytotoxic chemotherapy.
3. Active, uncontrolled infection or active systemic illness that requires
ongoing vasopressor support or mechanical ventilation.
4. Down syndrome.
5. Pregnancy.
6. Breast feeding.
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
8. Patients with congenital long QT syndrome, history of ventricular
arrhythmias or heart block.
9. Prior treatment with dasatinib, or any BCR-ABL1 inhibitor other than
imatinib.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-515499-12-00 |
| EudraCT | EUCTR2017-000705-20-NL |
| ClinicalTrials.gov | NCT03007147 |
| CCMO | NL64484.078.18 |