| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05327894 | Interfant-21 Treatment Protocol for Infants Under 1 Year With KMT2A-rearranged ALL or Mixed Phenotype Acute Leukemia | PHASE3 | RECRUITING | 160 | — | — | Dec 15, 2022 | Sep 1, 2030 | Apr 13, 2026 | 115 | Argentina, Australia +22 |
| NCT03476239 | Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) | PHASE3 | COMPLETED | 121 | — | — | Oct 18, 2017 | Apr 8, 2021 | Feb 8, 2023 | 23 | China |
| NCT04329325 | Blinatumomab and Tyrosine Kinase Inhibitor Therapy in People With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia | PHASE2 | ACTIVE NOT_RECRUITING | 17 | — | — | Mar 30, 2020 | Mar 1, 2027 | Apr 7, 2026 | 2 | United States |
| NCT02807883 | Blinatumomab Maintenance Following Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia | PHASE2 | COMPLETED | 23 | — | — | Aug 1, 2016 | Feb 1, 2022 | Jan 20, 2023 | 1 | United States |
| NCT01466179 | Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) | PHASE2 | COMPLETED | 225 | — | — | Dec 1, 2011 | Jan 1, 2017 | Aug 18, 2017 | 39 | United States, France +4 |
| NCT00560794 | Phase II Study of the BiTE® Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL) | PHASE2 | COMPLETED | 21 | — | — | Jan 1, 2008 | Nov 1, 2014 | Jan 26, 2015 | 6 | Germany |
| NCT04524455 | Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL | PHASE1 | COMPLETED | 17 | — | — | Oct 2, 2020 | Jan 24, 2023 | Apr 8, 2024 | 19 | United States, Australia +7 |
| NCT01471782 | Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia | PHASE1 | COMPLETED | 93 | — | — | Jan 1, 2012 | May 1, 2016 | Feb 8, 2017 | 30 | United States, Austria +5 |
The primary endpoint is EFS, defined as the time from diagnosis to resistance to induction, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up (censored) for patients without events.
A CR is defined as having ≤ 5% blasts in the bone marrow, no evidence of disease, and full recovery of peripheral blood counts (platelets \> 100,000/μL, and absolute neutrophil count \[ANC\] \> 1,000/μL). CRh\* is defined as ≤ 5% blasts in the bone marrow, no evidence of disease and partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl. CR/CRh\* rate is defined as the percentage of participants who achieve CR/CRh\* within 2 cycles of treatment with blinatumomab. Participants without response assessment were accounted for in the denominator when calculating the response rate, ie, these participants were counted as non-responders. The interim analysis was to become the primary analysis by meeting pre-specified efficacy and safety criteria based on an O'Brien-Fleming alpha spending function with the critical boundary 42.2%. Results for both the interim and final analysis are reported.
(MRD negativity by flow cytometry and quantitative PCR of BCR-ABL transcripts) at any time during TKI + corticosteroid induction or consolidation with up to 3 cycles of blinatumomab in combination with TKI.
Participants with treatment-related toxicities attributable to Blinatumomab. Toxicities defined as any 1) grade 3-4 acute GVHD greater than 30%, 2) secondary graft failure \>30%, or 3) nonrelapse mortality (NRM) within one cycle of Blinatumomab.
Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria: Complete Remission (CR): * bone marrow blasts ≤ 5% * no evidence of disease * full recovery of peripheral blood counts: * platelets \> 100,000/μL, and * absolute neutrophil count (ANC) \> 1,000/μL Complete Remission With Partial Hematological Recovery (CRh\*): * bone marrow blasts ≤ 5% * no evidence of disease * partial recovery of peripheral blood counts: * platelets \> 50,000/μL, and * ANC \> 500/μL.
MRD Response is defined as: * If Philadelphia Chromosome (Ph) positive (+) or translocation (t) (4;11), response was achieved when Ph or t(4;11) was below detection limit and individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4. * If Ph and t(4;11) negative, response was achieved when individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4.
Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.
A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that: * results in death, * immediately life-threatening, * requires in-patient hospitalization or prolongation of existing hospitalization, * results in persistent or significant disability/incapacity, * is a congenital anomaly/birth defect, and/or * other medically important serious AE. AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.
The maximum tolerated dose (MTD) was defined as one or fewer out of 6 participants experiencing a dose limiting toxicity (DLT) or the maximum administered dose (MAD). A dose limiting toxicity is any Grade ≥ 3 adverse event related to study drug, Grade 3 fatigue, headache, insomnia, fever, hypotension or infection were not considered dose limiting toxicities. Laboratory parameters of Grade ≥ 3 but not considered as clinically relevant and/or responding to routine medical management, thrombocytopenia, leukopenia (including neutropenia and lymphopenia), and anemia were not considered dose limiting toxicities.
Hematological assessments were performed from bone marrow biopsy samples. All hematological assessments of bone marrow were reviewed in a central laboratory. Complete remission (CR) was defined as * M1 bone marrow (bone marrow blasts \< 5%) * No evidence of circulating blasts or extra-medullary disease Complete remission includes participants with incomplete recovery of peripheral blood counts.
| Arm | Type | Description |
|---|---|---|
| Medium Risk (MR) | OTHER | Subject is defined as MR if \> 6months of age at diagnosis, OR \< 6 months of age with White Blood cell Count (WBC) \< 300 at diagnosis and good prednisone response. Subject gets 1st cycle of blinatumomab. If MRD is \>0.01%, after 1st cycle of blinatumomab, subject will be allocated to HR treatment from that phase, and will be eligible for HSCT. If MRD is undetectable or \< 0.01% after the 1st cycle of blinatumomab (TP2) patient will be eligible for replacement of MARMA by 2nd cycle of blinatumomab after receipt of lymphoid style consolidation (Protocol IB) or of myeloid style consolidation (ADE/MAE). |
| High risk (HR) | OTHER | Subject is defined as HR if \< 6 months of age with WBC \> 300 at diagnosis OR poor prednisone response. Also MR patients with end of induction MRD ≥ 1%, or MRD \> 0.01% after the 1st cycle of blinatumomab, will be allocated to HR treatment. Subject gets 1 cycle of blinatumomab. Thereafter patient is eligible for hematopoietic stem cell transplantation (HSCT) with or without experimental therapy in an investigational window. |
| Blinatumomab | EXPERIMENTAL | Treatment consisted of two induction cycles and up to 3 consolidation cycles of treatment for responders. In the first induction cycle, the initial dose of blinatumomab was 9 μg/day for Days 1-7 and then escalated (dose step) to 28 μg/day starting on day 8 (week 2) through day 29 (week 4). This is followed by two weeks without blinatumomab treatment. In subsequent cycles (beginning with the second induction cycle and continuing through consolidation, for applicable participants) 28 μg/day was administered for all 4 weeks of continuous treatment, followed by a treatment-free interval of two weeks. |
| Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI) | EXPERIMENTAL | Patients may receive steroids and hydroxyurea pre-study entry and receive a 7-day steroid prephase before starting TKI therapy. Planned initial TKI is dasatinib 140 mg daily; dasatinib dose may be reduced or TKI may be changed to a different agent under certain conditions. Induction consists of continuous TKI + 24 days of dexamethasone, followed by taper of dexamethasone, with bone marrow aspirate/biopsy (BMA) and CNS prophylaxis at days 22 and 43. Patients achieving morphologic complete response post-induction proceed to consolidation with up to 3 cycles of blinatumomab (28-day cycles, 14 days between cycles) + TKI, with BMA and CNS prophylaxis between cycles. Patients achieving complete molecular response may proceed to maintenance with up to 4 more cycles of blinatumomab (28-day cycles with 28 days between cycles) + TKI, with CNS prophylaxis between cycles and BMA after cycles 5 and 7. Patients can come off study to undergo allogeneic hematopoietic cell transplantation at any time. |
| Blinatumomab and AMG 404 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Blinatumomab | DRUG | 1st cycle: 15 μg/m2/day as a 4 week continuous IV infusion for patients with a M1 marrow. For patients with a M2/M3 marrow a step-dosing strategy is required with a dose of 5 μg/m2/day in week 1 followed by 15 μg/m2/day in weeks 2, 3, and 4. |
| Dexamthasone | DRUG | Premedication with dexamethasone was intended to prevent cytokine release syndrome (CRS) events associated with blinatumomab treatment. Treatment could start pre-study. Dexamethasone 20 mg IV was administered within 3 hours before start of blinatumomab in each treatment cycle, and within 3 hours before dose step increase. |
| dasatinib | DRUG | Please see detailed summary. |
| dexamethasone | DRUG | Please see detailed summary. |
| methotrexate | DRUG | Please see detailed summary. |
| Hematopoietic Cell Transplantation | PROCEDURE | Hematopoietic progenitor cell infusion |
| Blinatumomab (MT103) | BIOLOGICAL | Administered by continuous intravenous (CIV) over 4 weeks per cycle |
| AMG 404 | DRUG | AMG 404 will be administered as an intravenous infusion (IV). |
| Dexamethasone Premedication | DRUG | Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed. |
Inclusion Criteria: 1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement. 2. ≤ 365 days of age at the time of diagnosis of ALL. 3. ...