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GRAALL 2024 - A 3-cohort Randomized Study evaluating the role of New Immunotherapeutic Agents and of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Frontline Therapy of Adults with Acute Lymphoblastic Leukemia
EU CTIS ID: 2024-511437-35-00
What this study is testing
Primary objective GRAALL-2024/B o HR patients (phase 3): To improve the outcome of younger adults with HR Ph-negative BCP-ALL through early frontline incorporation of blinatumomab and refined indications for allogeneic HSCT. o SR patients (phase 2): To improve the outcome of younger adults with SR Ph-negative BCP-ALL through frontline incorporation of blinatumomab GRAALL-2024/T (phase 3): To improve the outcome of younger adults with T-ALL through early frontline incorporation of isatuximab GRAAPH-2024 (phase 3): To improve the outcome of younger adults with Ph-positive B-ALL through early frontline incorporation of blinatumomab, ponatinib, and refined indications for allogeneic HSCT.
- Phase II and Phase III (Integrated)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Patients aged 18 to 65 years old
- 2. Newly diagnosed ALL or T-LL according to the WHO criteria
- 3. Immunophenotypic, cytogenetic and/or FISH and molecular evaluation performed and allowing classifying the patient in one of the Phpos ALL, Phneg BCP-ALL or T-ALL cohorts
- 4. Not previously treated except with corticosteroids and/or intrathecal therapy (prephase)
- 5. ECOG performance status ≤2
- 6. Patient willing and able to understand the protocol requirements and comply with the treatment schedule, scheduled visits, electronic patient outcome reporting, exams and other requirements of the study
You likely can't join if
- 1. Patient previously treated with systemic chemotherapy for ALL, antibody-based therapy or TKI
- 10. Concurrent severe diseases which exclude the administration of therapy
- 11. Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
- 12. Pregnancy and breast feeding
- 13. Patients unwilling or unable to comply with the protocol
- 14. Patients under a legal protection regime (guardianship, trusteeship, judicial safeguard)
See the full eligibility criteria
- 1. Patients aged 18 to 65 years old
- 2. Newly diagnosed ALL or T-LL according to the WHO criteria
- 3. Immunophenotypic, cytogenetic and/or FISH and molecular evaluation performed and allowing classifying the patient in one of the Phpos ALL, Phneg BCP-ALL or T-ALL cohorts
- 4. Not previously treated except with corticosteroids and/or intrathecal therapy (prephase)
- 5. ECOG performance status ≤2
- 6. Patient willing and able to understand the protocol requirements and comply with the treatment schedule, scheduled visits, electronic patient outcome reporting, exams and other requirements of the study
- 7. Patients has signed written inform consent document
- 8. Willingness of women of child-bearing potential (WOCBP) and male subjects whose sexual partners are WOCBP to use an effective form of contraception, i.e. methods with a failure rate of <1% per year when used consistently and correctly, during the study and at least 6 months thereafter
- 9.Eligible for national health insurance (for french patients)
- 1. Patient previously treated with systemic chemotherapy for ALL, antibody-based therapy or TKI
- 10. Concurrent severe diseases which exclude the administration of therapy
- 11. Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
- 12. Pregnancy and breast feeding
- 13. Patients unwilling or unable to comply with the protocol
- 14. Patients under a legal protection regime (guardianship, trusteeship, judicial safeguard)
- 15. Chronic or current active uncontrolled infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
- 16. Current use of prohibited medication (see Section 7.11) (only GRAAPH)
- 17. Known hypersensitivity or severe reaction to ponatinib, blinatumomab, isatuximab or their excipients .
- 18. Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study
- 2. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
- 3. History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, coordination/movement disorder, autoimmune disease with CNS involvement, psychosis (with the exception of CNS leukemia that is well controlled with intrathecal therapy)
- 4. Patients with LVEF<50% or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
- 5. If patients with Phpos ALL (only GRAAPH): • Complete left bundle branch block, right bundle branch block plus left anterior hemiblock, bi-fascicular block • History of or presence of clinically significant ventricular or atrial tachyarrhythmias • Clinically significant resting bradycardia (< 50 beats per minute) • Congenital long QT syndrome or QTcF > 470 msec on screening ECG. If QTc > 470 msec and electrolytes are not within normal ranges before ponatinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion • Currently taking drug(s) that are known to have a risk of causing prolonged QTc or TdP unless the drug(s) can be changed to acceptable alternatives (ie, an alternate class of agents that do not affect the cardiac conduction system), or the participant can safely discontinue the drug(s) • Previous myocardial infarction within the last 12 months • Symptomatic peripheral vascular disease • History of ischemic stroke or transient ischemic attacks (TIAs) within the last 12 months • Significant bleeding disorder or thrombophilia unrelated to the underlying malignancy indication for study participation • Gastrointestinal disorders, such as malabsorption syndrome or any other illness that could affect oral absorption
- 6. Prior documented chronic liver disease. Inadequate hepatic functions defined as AST or ALT > 5 x the institutional upper limit of normal (ULN), or > 5 x ULN unless if considered due to leukemia. Total bilirubin > 1.5 x ULN unless if considered due to leukemia or Gilbert/Meulengracht
- 7. Estimated glomerular filtration rate (GFR) < 50 mL/mn using the MDRD equation
- 8. Chronic pancreatitis or acute pancreatitis within 6 months before study start
- 9. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C.
The study team makes the final eligibility decision.
Where it's taking place
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Switzerland. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.