Acute Lymphoblastic LeukemiaPhase 2/3GRAALL-2024NCT06860269
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
A Phase 2/3 study testing Randomization + Blinatumomab + chemotherapy, Randomization + Standard frontline T-ALL chemotherapy backbone and Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backbone in people with Acute Lymphoblastic Leukemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Adult acute lymphoblastic leukemia (ALL) includes Ph-positive (Phpos) ALL, Ph-negative (Phneg) B-cell precursor (BCP) ALL and T-ALL/lymphoblastic lymphoma (LL), accounting for approximately 25, 50 and 25% of all cases, respectively. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- Randomization + Blinatumomab + chemotherapy, Randomization + Standard frontline T-ALL chemotherapy backbone and Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backbone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,200 participants
- Where
- 1 siteFrance
- Study dates
- 6 May 2025to 15 Mar 2035
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18 to 65 years old
- Newly diagnosed ALL or T-LL according to the WHO criteria
- 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/LL cohorts
- Not previously treated except with corticosteroids and/or intrathecal therapy (prephase)
- Eligible for allo-HSCT if Phpos ALL or Phneg BCP-ALL
- ECOG performance status ≤2
Show all 10Show fewer
- 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
- Patients has signed written inform consent
- 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
- Eligible for National Health Insurance (for French patients)
Who cannot join
- Common exclusion criteria :
- Patient previously treated with systemic chemotherapy, antibody-based therapy or TKI
- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
- 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)
- Patients with LVEF<50% or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
- 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
Show all 29Show fewer
- Estimated glomerular filtration rate (GFR) < 50 mL/mn using the MDRD equation
- Chronic pancreatitis or acute pancreatitis within 6 months before study start
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or active infection with Hepatitis B or C.
- Concurrent severe diseases which exclude the administration of therapy
- Treatment with any other investigational agent or participating in another trial within 30 days prior to entering this study
- Pregnancy and breast feeding
- Patients unwilling or unable to comply with the protocol
- Patients under a legal protection regime (guardianship, trusteeship, judicial safeguard)
- Chronic or current active uncontrolled infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment
- Current use of prohibited medication
- Known hypersensitivity or severe reaction to ponatinib (GRAAPH), blinatumomab (GRAAPH and GRAALL-B) , isatuximab (GRAALL-T) or their excipients.
- Receipt of live (including attenuated) vaccines or anticipation of need for such vaccines during the study
- If patients with Phpos ALL:
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Saint Louis
Paris
Nicolas Boissel, MD, PhD, 0033142494949, nicolas.boissel@aphp.fr
About this study
Adult acute lymphoblastic leukemia (ALL) includes Ph-positive (Phpos) ALL, Ph-negative (Phneg) B-cell precursor (BCP) ALL and T-ALL/lymphoblastic lymphoma (LL), accounting for approximately 25, 50 and 25% of all cases, respectively. In younger adults, the results associated with standard therapy have markedly improved in these 3 groups, due to chemotherapy intensification in the BCP and T groups and addition of TKIs in the Phpos group, respectively. This led to reevaluate the role of allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, which is generally now indicated only in higher-risk patients, mostly defined as those with persistent high levels of minimal residual disease (MRD). Nevertheless, event-free survival (EFS) remains at 60-70% at 3 years, meaning there is still room for further improvements.
Fortunately, new immunotherapies have been approved to treat relapsed/refractory (R/R) BCP-ALL patients, including the anti-CD19 bispecific T-cell engager blinatumomab (BLINA, Blincyto®, Amgen). 4 BLINA is also approved for the frontline treatment of patients with persistent high measurable residual disease (MRD) levels after initial therapy (IG/TR MRD ≥0.1% (≥1.10-3
Read more
)). BLINA has been also evaluated frontline in combination with TKI in the Phpos group leading to promising outcome improvements. Toxicities associated with these combined treatments seem to be limited and manageable. In the Phpos ALL subset, the third-generation tyrosine kinase inhibitor ponatinib (PONA, Iclusig®, Incyte) has also been evaluated frontline with promising results when compared to 1st or even 2nd generation TKI. In the T-ALL/LL subset, anti-CD38 antibodies, approved to treat patients with multiple myeloma, are potential drugs of interest. The anti-CD38 antibody isatuximab (ISA, Sarclisa®, Immunogen, Sanofi-Aventis) is currently approved to treat myeloma patients in 2nd line. In vitro and in vivo preclinical studies suggest that CD38 is a relevant target in T-ALL and that isatuximab may be useful to eradicate residual disease in this subgroup of patients. Incorporation/combination of these new agents into frontline adult ALL therapy could allow reducing relapse incidence and prolonging survival in these patients, challenging the indication for HSCT in first complete remission (CR).
The present GRAALL-2024 study is a prospective multicenter multi-country 3-cohort randomized clinical trial.
The 3 cohorts are :
GRAALL-2024/B : Phneg BCP-ALL GRAAPH-2024 : Phpos ALL GRAALL-2024/T : T-ALL/LL
Eligible patients will be allocated to one on the 3 study cohorts during a common treatment prephase. The primary objective of the study is to improve the outcome of younger adults with ALL through optimal frontline incorporation of new antibody-based therapies, including BLINA in Phneg/pos BCP-ALL patients and ISA in T-ALL/LL patients, and to refine indication for allogeneic HSCT in first remission in Phneg/pos BCP-ALL patients.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- Randomization + Blinatumomab + chemotherapy, Randomization + Standard frontline T-ALL chemotherapy backbone, Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backbone, Randomization + Blinatumomab + Ponatinib + chemotherapy, Randomization 1 + Allo HSCT
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Randomization + Blinatumomab + chemotherapyDrug
Rando 1 : BLINA will be given at 28 µg/day IVC from D1 to D28 for 2 to 4 cycles (first cycle starts with 9 µg/day for 7 days)
Randomization + Standard frontline T-ALL chemotherapy backboneOther
Rando 3 : standard of care
Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backboneDrug
Rando 3 : ISA will be given at 10 mg/kg IV for a maximum of 28 infusions starting at induction up to maintenance phase.
Randomization + Blinatumomab + Ponatinib + chemotherapyDrug
Rando 2 :
- PONA will be given at 45 mg/day PO during 2 cycles, 30 mg/day during 2 additional cycles, and 15 mg/day during maintenance phase or after alloHSCT
- BLINA will be given at 28 µg/day IVC from D1 to D28 for 2 to 5 cycles (first cycle starts with 9 µg/day for 7 days). Patients allografted will receive two courses before transplant.
Randomization 1 + Allo HSCTOther
Rando 1 : standard of care - Allogeneic Hematopoietic Stem Cell Transplantation
Randomization 2 + Allo HSCTOther
Rando 2 : standard of care
| Study group | Role | What they receive |
|---|---|---|
| GRAALL-2024/B Very High Risk - SOC | No intervention | Phneg BCP-ALL cohort Standard of Care : ALLO HSCT |
| GRAALL-2024/B High Risk - SOC | Active comparator | Phneg BCP-ALL cohort Receives: Other: Randomization 1 + Allo HSCT |
| GRAALL-2024/B High risk - Blina | Experimental | Phneg BCP-ALL cohort Receives: Drug: Randomization + Blinatumomab + chemotherapy |
| GRAALL-2024/B Standard Risk - SOC | No intervention | Phneg BCP-ALL cohort Standard of Care : Blinatumomab + chemotherapy |
| GRAALL-2024/T - SOC | Active comparator | T-ALL cohort Receives: Other: Randomization + Standard frontline T-ALL chemotherapy backbone |
| GRAALL-2024/T - Isa | Experimental | T-ALL cohort Receives: Drug: Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backbone |
| GRAAL-2024/T - T-cell lymphoblastic lymphoma - SOC | No intervention | Non randomized - standard care |
| GRAAPH-2024 - SOC | Active comparator | Phpos ALL cohort Receives: Other: Randomization 2 + Allo HSCT |
| GRAAPH-2024 - Blina/Pona | Experimental | Phpos ALL cohort Receives: Drug: Randomization + Blinatumomab + Ponatinib + chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
For GRAAL-2024/B HR patients (phase 3)
Measured: At 5 years
Overall survival
For GRAAL-2024/B SR patients (phase 2)
Measured: At 5 years
Event-Free Survival
For GRAAL-2024/T patients (phase 3)
Measured: At 5 years
Overall survival
For GRAAPH-2024 patients (phase 3) - Phpos ALL
Measured: At 5 years
Secondary outcomes (20)
Overall survival
in the T-ALL/LL cohorts
Measured: At 5 years
Event Free Survival
Measured: At 5 years
Relapse Free Survival
Measured: At 5 years
Hematological complete response rate
After induction
Measured: At 45 days
Hematological complete response rate
After consolidation
Measured: At 4 months
Measurable residual disease (MRD) response level
(IG/TR and BCR::ABL1 markers) at diagnosis
Measured: At inclusion
Measurable residual disease (MRD) response level - non graft patients
(IG/TR and BCR::ABL1 markers) After each treatment cycle until maintenance (4 to 5 times)
Measured: Up to 6 months
Measurable residual disease (MRD) response level - graft patients
(IG/TR and BCR::ABL1 markers) At day 100 post-HSCT and every 3 months post HSCT for patients receiving allo-HSCT during maintenance up to 2 years
Measured: Through study completion, approximately 5 years
Measurable residual disease (MRD) response level
(IG/TR and BCR::ABL1 markers) At relapse
Measured: Up to 5 years
Early mortality
Measured: At day 30
Early mortality
Measured: At day 60
Early mortality
Measured: At day 90
Cumulative incidence of relapse (CIR)
Measured: At 5 years
Cumulative incidence of non relapse mortality
Measured: At 5 years
Transplant-related mortality (TRM)
For graft patients
Measured: At 5 years
Graft-versus-host-disease (GvHD) incidence
For graft patients
Measured: At 5 years
Number of patients who experience one or more Adverse Event (AEs) or Serious Adverse Event (SAEs)
Measured: At 5 years
Rate of patients who experience one or more Adverse Event (AEs) or Serious Adverse Event (SAEs)
Measured: At 5 years
Quality of life level
Assessed with EQ5D 5L It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life.
At each study visit
Measured: Until 5 years
Incremental cost effectiveness and cost utility ratio
Defined as the difference in total costs divided by the difference in survival and in quality adjusted life years
Measured: At 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start6 May 2025
- Primary completion15 Mar 2035 (estimated)
- Study completion15 Mar 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 3-cohort stratified multicenter multi-country prospective open-label randomized Phase III trial. In each cohort, participants will be randomized according to a 1:1 ratio (R1, R2 and R3). Additionnally a phase 2 single arm trial will be performed in SR patients of the Phneg BCP-ALL cohort. Of note, T-LL patients will be included but not randomized to receive ISA or not.
- Masking
- None (open label)
- Enrolment
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06860269
- Sponsor's protocol ID
- APHP210356
- Acronym
- GRAALL-2024
- Status last verified
- Feb 2026
- First submitted
- 16 Jan 2025
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06860269
- Acronym / sponsor ID
- GRAALL-2024 / APHP210356
- Conditions
- Acute Lymphoblastic Leukemia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 6 May 2025 (actual)
- Primary completion
- 15 Mar 2035 (estimated)
- Study completion
- 15 Mar 2035 (estimated)
- First posted
- 6 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adult acute lymphoblastic leukemia (ALL) includes Ph-positive (Phpos) ALL, Ph-negative (Phneg) B-cell precursor (BCP) ALL and T-ALL/lymphoblastic lymphoma (LL), accounting for approximately 25, 50 and 25% of all cases, respectively. In younger adults, the results associated with standard therapy have markedly improved in these 3 groups, due to chemotherapy intensification in the BCP and T groups and addition of TKIs in the Phpos group, respectively. This led to reevaluate the role of allogeneic hematopoietic stem cell transplantation (HSCT) in first remission, which is generally now indicated only in higher-risk patients, mostly defined as those with persistent high levels of minimal residual disease (MRD). Nevertheless, event-free survival (EFS) remains at 60-70% at 3 years, meaning there is still room for further improvements.
Fortunately, new immunotherapies have been approved to treat relapsed/refractory (R/R) BCP-ALL patients, including the anti-CD19 bispecific T-cell engager blinatumomab (BLINA, Blincyto®, Amgen). 4 BLINA is also approved for the frontline treatment of patients with persistent high measurable residual disease (MRD) levels after initial therapy (IG/TR MRD ≥0.1% (≥1.10-3
)). BLINA has been also evaluated frontline in combination with TKI in the Phpos group leading to promising outcome improvements. Toxicities associated with these combined treatments seem to be limited and manageable. In the Phpos ALL subset, the third-generation tyrosine kinase inhibitor ponatinib (PONA, Iclusig®, Incyte) has also been evaluated frontline with promising results when compared to 1st or even 2nd generation TKI. In the T-ALL/LL subset, anti-CD38 antibodies, approved to treat patients with multiple myeloma, are potential drugs of interest. The anti-CD38 antibody isatuximab (ISA, Sarclisa®, Immunogen, Sanofi-Aventis) is currently approved to treat myeloma patients in 2nd line. In vitro and in vivo preclinical studies suggest that CD38 is a relevant target in T-ALL and that isatuximab may be useful to eradicate residual disease in this subgroup of patients. Incorporation/combination of these new agents into frontline adult ALL therapy could allow reducing relapse incidence and prolonging survival in these patients, challenging the indication for HSCT in first complete remission (CR).
The present GRAALL-2024 study is a prospective multicenter multi-country 3-cohort randomized clinical trial.
The 3 cohorts are :
GRAALL-2024/B : Phneg BCP-ALL GRAAPH-2024 : Phpos ALL GRAALL-2024/T : T-ALL/LL
Eligible patients will be allocated to one on the 3 study cohorts during a common treatment prephase. The primary objective of the study is to improve the outcome of younger adults with ALL through optimal frontline incorporation of new antibody-based therapies, including BLINA in Phneg/pos BCP-ALL patients and ISA in T-ALL/LL patients, and to refine indication for allogeneic HSCT in first remission in Phneg/pos BCP-ALL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
- Model description
- 3-cohort stratified multicenter multi-country prospective open-label randomized Phase III trial. In each cohort, participants will be randomized according to a 1:1 ratio (R1, R2 and R3). Additionnally a phase 2 single arm trial will be performed in SR patients of the Phneg BCP-ALL cohort. Of note, T-LL patients will be included but not randomized to receive ISA or not.
| Arm | Type | Receives |
|---|---|---|
| GRAALL-2024/B Very High Risk - SOC | No intervention | –Phneg BCP-ALL cohort Standard of Care : ALLO HSCT |
| GRAALL-2024/B High Risk - SOC | Active comparator | Other: Randomization 1 + Allo HSCTPhneg BCP-ALL cohort |
| GRAALL-2024/B High risk - Blina | Experimental | Drug: Randomization + Blinatumomab + chemotherapyPhneg BCP-ALL cohort |
| GRAALL-2024/B Standard Risk - SOC | No intervention | –Phneg BCP-ALL cohort Standard of Care : Blinatumomab + chemotherapy |
| GRAALL-2024/T - SOC | Active comparator | Other: Randomization + Standard frontline T-ALL chemotherapy backboneT-ALL cohort |
| GRAALL-2024/T - Isa | Experimental | Drug: Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backboneT-ALL cohort |
| GRAAL-2024/T - T-cell lymphoblastic lymphoma - SOC | No intervention | –Non randomized - standard care |
| GRAAPH-2024 - SOC | Active comparator | Other: Randomization 2 + Allo HSCTPhpos ALL cohort |
| GRAAPH-2024 - Blina/Pona | Experimental | Drug: Randomization + Blinatumomab + Ponatinib + chemotherapyPhpos ALL cohort |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients aged 18 to 65 years old
- Newly diagnosed ALL or T-LL according to the WHO criteria
- 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/LL cohorts
- Not previously treated except with corticosteroids and/or intrathecal therapy (prephase)
- Eligible for allo-HSCT if Phpos ALL or Phneg BCP-ALL
Key exclusion criteria (29 listed)
- Patient previously treated with systemic chemotherapy, antibody-based therapy or TKI
- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
- 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)
- Patients with LVEF<50% or other clinically significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Randomization + Blinatumomab + chemotherapyRando 1 : BLINA will be given at 28 µg/day IVC from D1 to D28 for 2 to 4 cycles (first cycle starts with 9 µg/day for 7 days) | Drug | GRAALL-2024/B High risk - Blina |
| Randomization + Standard frontline T-ALL chemotherapy backboneRando 3 : standard of care | Other | GRAALL-2024/T - SOC |
| Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backboneRando 3 : ISA will be given at 10 mg/kg IV for a maximum of 28 infusions starting at induction up to maintenance phase. | Drug | GRAALL-2024/T - Isa |
| Randomization + Blinatumomab + Ponatinib + chemotherapyRando 2 : * PONA will be given at 45 mg/day PO during 2 cycles, 30 mg/day during 2 additional cycles, and 15 mg/day during maintenance phase or after alloHSCT * BLINA will be given at 28 µg/day IVC from D1 to D28 for 2 to 5 cycles (first cycle starts with 9 µg/day for 7 days). Patients allografted will receive two courses before transplant. | Drug | GRAAPH-2024 - Blina/Pona |
| Randomization 1 + Allo HSCTRando 1 : standard of care - Allogeneic Hematopoietic Stem Cell Transplantation | Other | GRAALL-2024/B High Risk - SOC |
| Randomization 2 + Allo HSCTRando 2 : standard of care | Other | GRAAPH-2024 - SOC |
Primary outcome
Overall survival
Time frame: At 5 years
For GRAAL-2024/B HR patients (phase 3)
Overall survival
Time frame: At 5 years
For GRAAL-2024/B SR patients (phase 2)
Event-Free Survival
Time frame: At 5 years
For GRAAL-2024/T patients (phase 3)
Overall survival
Time frame: At 5 years
For GRAAPH-2024 patients (phase 3) - Phpos ALL
20 secondary outcomes
Overall survival
Time frame: At 5 years
Event Free Survival
Time frame: At 5 years
Relapse Free Survival
Time frame: At 5 years
Hematological complete response rate
Time frame: At 45 days
Hematological complete response rate
Time frame: At 4 months
Measurable residual disease (MRD) response level
Time frame: At inclusion
Measurable residual disease (MRD) response level - non graft patients
Time frame: Up to 6 months
Measurable residual disease (MRD) response level - graft patients
Time frame: Through study completion, approximately 5 years
Measurable residual disease (MRD) response level
Time frame: Up to 5 years
Early mortality
Time frame: At day 30
Early mortality
Time frame: At day 60
Early mortality
Time frame: At day 90
Cumulative incidence of relapse (CIR)
Time frame: At 5 years
Cumulative incidence of non relapse mortality
Time frame: At 5 years
Transplant-related mortality (TRM)
Time frame: At 5 years
Graft-versus-host-disease (GvHD) incidence
Time frame: At 5 years
Number of patients who experience one or more Adverse Event (AEs) or Serious Adverse Event (SAEs)
Time frame: At 5 years
Rate of patients who experience one or more Adverse Event (AEs) or Serious Adverse Event (SAEs)
Time frame: At 5 years
Quality of life level
Time frame: Until 5 years
Incremental cost effectiveness and cost utility ratio
Time frame: At 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Randomization + Blinatumomab + chemotherapy, Randomization + Standard frontline T-ALL chemotherapy backbone and Randomization + Isatuximab + Standard frontline T-ALL chemotherapy backbone in people with Acute Lymphoblastic Leukemia, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicolas Boissel, MD PhD (1 42 49 96 43 ext. +33, nicolas.boissel@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: At 5 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.