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This is a prospective, open-label, non-randomized cohort study evaluating the efficacy and safety of a pediatric-inspired chemotherapy regimen (IH-2014 based) combined with venetoclax and immunotherapy in adult patients with newly diagnosed Ph-negative Acute Lymphoblastic Leukemia (ALL). Patients aged ≥14years,≤60 years will be enrolled. Treatment includes induction, consolidation, early intensification, delayed intensification, and maintenance phases. The use and number of cycles of immunotherapy will be based on patient preference. The primary endpoint is Event-Free Survival (EFS) and MRD-negative CR rates after induction therapy(by flow cytometry and NGS). Secondary endpoints include Complete Remission (CR) rate, MRD-negative CR rates at 12 weeks (by flow cytometry and NGS), Overall Survival (OS), Relapse-Free Survival (RFS), and cumulative relapse rate.
Adult Ph-negative ALL has inferior outcomes compared to childhood ALL. Pediatric-inspired regimens have improved survival in adolescent and young adult (AYA) patients. Venetoclax, a BCL-2 inhibitor, has shown preclinical sensitivity in Ph-negative ALL. Our center's previous IH-2022 regimen (a pediatric-inspired regimen combined with venetoclax protocol) showed promising efficacy and tolerability in adult patients.Immunotherapy is effective in ALL. This study aims to integrate immunotherapy into the pediatric-inspired backbone to optimize the regimen and improve survival outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chemotherapy induction Arm | Experimental | Induction Regimen 1 (VDCLP+V): Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax. Patients with either CD22-negative or CD22-positive B-ALL will receive this regimen. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction. |
|
| Immunotherapy induction Arm | Experimental | Induction Regimen 2 (2VIP): Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone. For patients with CD22-positive B-ALL (≥20% blasts), especially those aged >55 years, the 2VIP regimen is recommended. Consolidation Therapy: Based on the pediatric-inspired IH-2022 protocol, including Vincristine , Daunorubicin , Cyclophosphamide, Pegaspargase , Prednisone, Dexamethasone, Cytarabine, 6-Mercaptopurine , and High-Dose Methotrexate. Immunotherapy: Blinatumomab - optional, 1 to 4 cycles, starting post-induction, alternating with chemotherapy cycles. CAR-T Cell Therapy- optional: the third cycle. Maintenance Therapy: Consists of a monthly MM regimen and a VP plus Venetoclax regimen every 3 months. CNS Prophylaxis Allogeneic or autologous Hematopoietic Stem Cell Transplantation is considered for high-risk patients or those with positive MRD after induction. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VDCLP+V | Drug | Vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, and venetoclax. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Event-Free Survival | up to 5 years | |
| MRD-negative CR rate by flow cytometry after induction regimen | up to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Remission Rate | up to 1 year | |
| MRD-negative CR rate by flow cytometry at 12 weeks | up to 12 weeks | |
| MRD-negative CR rate by NGS at 12 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hui Wei, Doctor | Contact | 13132507161 | weihui@ihcams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Blood Diseases Hospital | Recruiting | Tianjin | Tianjin Municipality | 300020 | China |
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| 2VIP | Drug | Inotuzumab ozogamicin, venetoclax, vincristine, and prednisone. |
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| Consolidation Therapy | Drug | Includes vincristine, daunorubicin, cyclophosphamide, pegaspargase, prednisone, dexamethasone, cytarabine, 6-mercaptopurine, and high-dose methotrexate. |
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| Maintenance Therapy | Drug | Monthly MM regimen (6-mercaptopurine and methotrexate) and every 3 months VP (vincristine and prednisone) plus venetoclax. |
|
| Blinatumomab | Drug | Optional; 1 to 4 cycles (28 days each) based on patient choice, starting post-induction, alternating with chemotherapy cycles. |
|
| Venetoclax | Drug | Oral targeted therapy administered during induction, consolidation, and maintenance phases as per protocol |
|
| CNS Prophylaxis | Procedure | Intrathecal injection (methotrexate, cytarabine, dexamethasone) for a total of at least 15 sessions. Prophylactic cranial irradiation (18 Gy) is an alternative for patients unable or unwilling to receive intrathecal injections. |
|
| CAR-T Cell Therapy | Procedure | Preconditioning regimen with fludarabine and cyclophosphamide (FC) administered after the third course (second consolidation) for patients receiving CAR-T. |
|
| Hematopoietic Stem Cell Transplantation (HSCT) | Procedure | Allogeneic or autologous HSCT considered for high-risk patients or those with positive MRD after induction in CR1, provided a suitable donor is available. |
|
| up to 12 weeks |
| Overall Survival (OS) | Up to 5 years |
| Relapse-Free Survival (RFS) | Up to 5 years |
| Cumulative Incidence of Relapse | Up to 5 years |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D008283 | Maintenance |
| C510808 | blinatumomab |
| C579720 | venetoclax |
| D016219 | Immunotherapy, Adoptive |
| D018380 | Hematopoietic Stem Cell Transplantation |
| ID | Term |
|---|---|
| D005159 | Health Care Facilities Workforce and Services |
| D019264 | Adoptive Transfer |
| D007116 | Immunization, Passive |
| D007114 | Immunization |
| D007167 | Immunotherapy |
| D056747 | Immunomodulation |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D007158 | Immunologic Techniques |
| D008919 | Investigative Techniques |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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