BLINATUMOMAB for Acute lymphoblastic leukaemia (ALL)|CD19-positive B-cell acute lymphoblastic leukaemia

Inclusion criteria

• {"criterion_text":"- Inclusion Criteria applicable to All the patients •\tMale and female patients with allogenic transplant indication for ALL, as determined by national frontline protocols, including but not limited to: o\tAIEOP-BFM ALL 2017 or 2025 o\tALLTogether o\tALL-IC o\tIntReALL 2020 o\tESPhall-COG o\tInterfant 2021 o\tOther recognized national frontline protocols. •\tAge ≥3 months to ≤25 years at the time of HSCT. •\tPatients must be in complete remission (with <5% blasts and absence of leukemia cells in extramedullary sites) prior to undergoing HSCT. •\tSelected donor must be either a matched donor (matched donor category includes 9/10 identical siblings and 10/10 or 9/10 HLA-matched unrelated donors) or a mismatched family donor (≤8/10 HLA match). Both bone marrow or peripheral blood stem cell grafts are permitted. Cord blood is permitted, as well, provided that the unit is at least 6/8 HLA matched and with a cryopreserved cellularity of at least 3x107 nucleated cells/Kg recipient body weight. •\tFemale patients of childbearing potential must have a negative pregnancy test at screening, and all patients must agree to adhere to effective contraception during the study period. •\tWritten study informed consent and/or assent from the patient and/or the parent, or guardian at the time of screening. •\tNo history of other malignancies."}
• {"criterion_text":"- R1 Sub-Study \tInclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients ≥2 years to ≤ 25 years of age at the time of informed consent. •\tSelected donor must be a matched donor (matched donor category includes 10/10 identical siblings and 10/10 or 9/10 HLA-matched unrelated donors). Both bone marrow or peripheral stem cell grafts are permitted. Related donor cord blood is permitted, as well, if the unit has a cryopreserved cellularity of at least 3x107 nucleated cells/Kg recipient body weight. •\tWritten study informed consent and/or assent from the patient and the parent or guardian at the time of screening. •\tFulfilment of the inclusion criteria of the FORUM 2 platform trial"}
• {"criterion_text":"- R2 Sub-Study Inclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients ≥3 months to < 18 years of age at the time of informed consent. •\tPatients who have received an unmanipulated allogeneic bone marrow or peripheral blood transplant from a matched donor (matched donor category includes ≥9/10 related or unrelated donors). Recipients of either TBI-based (irrespective of the intensity) or chemo- conditioning regimens are eligible. •\tClinically suspected grade II to IV aGVHD as per MAGIC criteria, occurring after allo-HSCT. Biopsy confirmation of aGvHD is recommended whenever possible but is not mandatory. Enrollment should not be delayed awaiting biopsy or pathology results and, in cases where a biopsy cannot be obtained or is clinically contraindicated, clinical suspicion of acute GVHD by the treating physician is sufficient, provided that alternative diagnoses are adequately ruled out. •\tEvidence of myeloid engraftment (ANC ≥ 0.5 × 109/L for 3 consecutive days). Use of growth factor supplementation is allowed. •\tAble to swallow and retain oral medication. •\tWritten study informed consent and/or assent from the patient and the parent or guardian at the time of screening"}
• {"criterion_text":"- S1 Sub-Study Inclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients ≥3 months to ≤25 years of age at the time of informed consent. •\tSelected donor must be a mismatched family donor (≤8/10 HLA match). •\tGvHD prophylaxis based on either in-vivo PTCy or ex vivo αβ T-Cell depletion. •\tUse of the conditioning regimens specified in the specific study. •\tWritten study informed consent and/or assent from the patient and the parent or guardian at the time of screening"}
• {"criterion_text":"- P1 Sub-Study Inclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients < 2 years of age at HSCT •\tEvidence of CD19 expression on leukemia blasts prior to HSCT. Previous treatment with blinatumomab and any other CD19-directed immunotherapy during front-line treatment before the allograft is not considered an exclusion criterion. •\tPatients who have received an allogeneic bone marrow or peripheral blood HSCT from a matched donor (matched donor category includes ≥9/10 related or unrelated donors) or mismatched related donors (i.e., HLA-hapoidentical donor). •\tMorphological bone marrow complete remission at time of enrollment, independently from MRD levels (both before and after HSCT) and independently from the presence of recurrent molecular lesions, such as KMT2A rearrangements. •\tNo evidence of CNS active disease (i.e., CNS1) or any extramedullary localization of leukemia cells at time of study enrolment. Patients with previous CNS leukemia involvement are eligible if CNS was successfully treated prior to enrollment. •\tWritten study informed consent and/or assent from the patient and/or the parent, or guardian at the time of screening"}
• {"criterion_text":"- O1 Sub-Study Inclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients ≥3 months to ≤25 years of age at the time of informed consent. •\tWritten study informed consent and/or assent from the patient and the parent or guardian at the time of screening"}
• {"criterion_text":"- O2 Sub-Study Inclusion Criteria •\tSubjects enrolled in the FORUM2 platform trial. •\tPatients ≥3 months to ≤25 years of age at the time of informed consent. •\tPatients expected to receive bone marrow allografts with ABO major incompatibility from either matched donors or mismatched family donors •\tWritten study informed consent and/or assent from the patient and the parent or guardian at the time of screening"}

Exclusion criteria

• {"criterion_text":"- Exclusion Criteria applicable to all the patients •\tPatients < 3 months and > 25 years of age at the time of HSCT. •\tPatients not in complete morphological remission at the time of enrollment. •\tPatients with an initial diagnosis of Non-Hodgkin Lymphoma (NHL). •\tPatients with ALL as a secondary malignancy. •\tPatients with a history of previous autologous or allogeneic HSCT (prior allogeneic transplantation is permitted for subjects receiving post-transplant interventions, such as those enrolled in the R2 and P1 study, provided that this is their first allogeneic HSCT). •\tFemale patients who are pregnant or breast feeding. •\tFertile male or female patients of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of contraception. •\tActive clinically uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no physical or radiographic signs of infection progression are present. •\tActive HBV or HCV infection that requires treatment, or at risk for HBV reactivation (ie, positive HBsAg). Subjects with negative HbsAg and positive total HB core antibody may be included if HBV DNA is undetectable at the time of screening. Subjects who are positive for HCV antibody are eligible only if polymerase chain reaction test is negative for HCV RNA. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment. Prior serology results are acceptable for determining eligibility. •\tKnown human immunodeficiency virus infection (HIV). •\tSignificant respiratory disease including patients who are on mechanical ventilation or who have resting O2 saturation <90% by pulse-oximetry on room-air. •\tPresence of severely impaired renal function (confirmed within 72 hrs prior to study treatment start) defined by: o\tGlomerular Filtration Rate (GFR) < 30 mL/min/1.73 m2 using estimated creatinine clearance calculated by updated bedside Schwartz equation or Cockroft Gault equation •\tOr o\tRenal dialysis requirement •\tClinically significant or uncontrolled cardiac disease including any of the following: o\t- Uncontrolled hypertension o\t- New York Heart Association Class III or IV congestive heart failure o\t- Clinically significant cardiac arrhythmias •\tSevere hepatic insufficiency, defined by any of the following: o\tChild-Pugh Class C liver disease o\tAST (aspartate aminotransferase) or ALT (alanine aminotransferase) levels > 5 times the upper limit of normal (ULN), unless attributable to GvHD o\tTotal bilirubin > 3.0 mg/dL, unless attributable to GvHD o\tINR (International Normalized Ratio) ≥ 1.7 o\tClinical evidence of hepatic encephalopathy or ascites •\tPresence of severe concomitant constitutional disease that precludes treatment as per protocol, based on the investigator’s judgment. Examples include but are not limited to: Down syndrome with severe comorbidities, significant cardiac malformations, metabolic disorders affecting treatment feasibility. •\tUnderlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere participation in the study, pose a significant risk to the patient or interfere with interpretation of study data. •\tKarnofsky or Lansky performance score <50%, indicating significant functional impairment. •\tPatients who are unwilling or unable to comply with study procedures, including follow-up requirements and treatment schedules."}
• {"criterion_text":"- R1 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason). •\tPatients <2 years or > 25 years of age at the time of informed consent. •\tUse of an unrelated cord blood unit or a mismatched family donor as the stem cell source •\tPatients who received CNS irradiation at a dose of 18 Gy within 12 months prior to HSCT, if the combined total dose from prior CNS irradiation and planned TBI conditioning will exceed 24 Gy. •\tPatient meets one or more of the exclusion criteria defined in the FORUM 2 platform trial"}
• {"criterion_text":"- R2 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason) •\tPatients <3 months of age or ≥ 18 years. •\tPatients transplanted from mismatched family donor (≤8/10 HLA match) or related/unrelated CB. •\tPatients having received any prior systemic treatment of aGvHD except for a maximum 72h of prior systemic corticosteroid therapy after the onset of acute GvHD. Patients are allowed to have received prior GvHD prophylaxis which is not counted as systemic treatment (as long as the prophylaxis was started prior to the diagnosis of aGvHD) •\tClinical presentation resembling de novo chronic GvHD or GvHD overlap syndrome with both acute and chronic GvHD features •\tFailed prior allogeneic HSCT, including previous primary or secondary graft failure •\tAcute GvHD occurring after non-scheduled donor leukocyte infusion (DLI) administered for pre-emptive treatment of malignancy recurrence. •\tPresence of overt relapse of primary malignancy, requiring either additional treatment after allogeneic HSCT or rapid immune suppression tapering/withdrawal •\tAny corticosteroid therapy for indications other than GVHD at doses > 1 mg/kg per day methylprednisolone (or prednisone equivalent) within 7 days of randomization. •\tCholestatic disorders, or unresolved sinusoidal obstructive syndrome/veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to aGvHD and ongoing organ dysfunction). •\tKnown allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds."}
• {"criterion_text":"- S1 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason) •\tPatients <3 months or > 25 years of age at the time of informed consent. •\tAny type of GvHD prophylaxis other than in-vivo PTCy or ex vivo αβ T-Cell depletion"}
• {"criterion_text":"- P1 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason) •\tPatients ≥ 2 years of age at HSCT •\tPatients not in complete remission at the time of enrollment •\tPresence of transplant-associated thrombotic microangiopathy •\tPrevious diagnosis of SOS/VOD not resolved since at least 3 weeks before study inclusion •\tPresence of idiopathic pneumonia syndrome •\tOngoing immunosuppression for reasons other than standard GVHD prophylaxis •\tPatients who received TBI as part of their conditioning regimen or a chemotherapy-based conditioning regimen other than busulfan, thiotepa and fludarabine or treosulfan, thiotepa and fludarabine or busulfan and cyclophosphamide (±VP16). •\tPresence of active grade III-IV acute GVHD at the time of enrollment. •\tPresence of grade II acute GVHD with either gastrointestinal or liver involvement. •\tClinically relevant active infections, including unresolved bacterial, fungal, or parasitic infections or active uncontrolled viral reactivations (e.g., CMV, EBV, or adenovirus). •\tANC <0.5 × 109/L or self-sustained platelet count <30 x 109/L at time of study enrolment, •\tCreatinine clearance lower than 30 ml/min or serum bilirubin > 3 x ULN prior to start of treatment (unless related to Gilbert’s or Meulengracht disease). •\tLansky performance status < 50. •\tPatients transplanted from related/unrelated CB."}
• {"criterion_text":"- O1 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason) •\tPatients <3 months or > 26 years of age at the time of informed consent."}
• {"criterion_text":"- O2 Sub-Study Exclusion Criteria •\tPatients not enrolled in the FORUM 2 platform trial (independently of the reason) •\tPatients <3 months or > 25 years of age at the time of informed consent. •\tGraft source represented by peripheral blood stem cells"}

Primary endpoints

• {"endpoint_text":"- R1 Sub-Study: The primary endpoint is Event Free Survival (EFS) at year 4. EFS is defined as the time from randomization (intention-to-treat analysis) or HSCT (per-protocol/as treated) to first failure event defined as follows: Failure events are: •\tRelapse •\tDeath from any cause •\tDiagnosis of a second malignant neoplasm Patients without event will be censored at last follow-up date.","definition_or_measurement_approach":"EFS measured from randomization (ITT) or HSCT (per-protocol) to first failure event (relapse, death from any cause, diagnosis of second malignant neoplasm); patients without event censored at last follow-up."}
• {"endpoint_text":"- R2 Sub-Study: •\tOverall response rate (ORR) at Day 28 after randomization, defined as the proportion of patients in each arm demonstrating a complete response (CR) or partial response (PR) without requirement for additional systemic therapies for earlier progression, mixed response or nonresponse. Scoring of response will be relative to the organ stage at the time of randomization.","definition_or_measurement_approach":"ORR at Day 28 after randomization: proportion with CR or PR without need for additional systemic therapies; response scored relative to organ stage at randomization."}
• {"endpoint_text":"- S1 Sub-Study: EFS is defined as the time from HSCT to first failure event defined as follows: Failure events are: -\tRelapse -\tGraft failure -\tDeath from any cause -\tDiagnosis of a second malignant neoplasm Patients without event will be censored at last follow-up date.","definition_or_measurement_approach":"EFS measured from HSCT to first failure event (relapse, graft failure, death from any cause, diagnosis of second malignant neoplasm); censoring at last follow-up if no event."}
• {"endpoint_text":"- P1 Sub-Study: Compare the CIR 2 years after HSCT in blinatumomab-treated patents and historical controls. CIR is calculated from the time of study enrolment until the date of relapse (defined as either bone marrow aspirate or biopsy with ≥ 5% blasts or as appearance of leukemia cells in an extramedullary site) or last follow-up (death from any cause other than leukemia relapse will be considered a competing event).","definition_or_measurement_approach":"Cumulative incidence of relapse (CIR) at 2 years after HSCT, calculated from enrolment until relapse (bone marrow ≥5% blasts or extramedullary disease) or last follow-up; death from other causes treated as competing event."}

Germany

Earliest CTIS Part Ii Submission Date

06-11-2025

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

165

Number Of Sites

25

Number Of Participants

180

Austria

Earliest CTIS Part Ii Submission Date

06-11-2025

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

162

Number Of Sites

3

Number Of Participants

40

Czechia

Earliest CTIS Part Ii Submission Date

21-10-2025

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

178

Number Of Sites

1

Number Of Participants

40

Denmark

Earliest CTIS Part Ii Submission Date

28-10-2025

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

169

Number Of Sites

1

Number Of Participants

20

Finland

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

180

Number Of Sites

1

Number Of Participants

40

France

Earliest CTIS Part Ii Submission Date

27-10-2025

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

170

Number Of Sites

17

Number Of Participants

150

Italy

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

14-04-2026

Processing Time Days

179

Number Of Sites

9

Number Of Participants

120

Norway

Earliest CTIS Part Ii Submission Date

09-10-2025

Latest Decision Or Authorization Date

15-04-2026

Processing Time Days

188

Number Of Sites

1

Number Of Participants

25

Poland

Earliest CTIS Part Ii Submission Date

03-11-2025

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

168

Number Of Sites

7

Number Of Participants

120

Primary sponsor

Full Name

Ospedale Pediatrico Bambino Gesu

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"Denmark","full_name":"Region Hovedstaden","duties_or_roles":"sponsorDuties code 1; contact email: gcp-enheden.bispebjerg-frederiksberg-hospitaler@regionh.dk","organisation_type":"Hospital/Clinic/Other health care facility"}