Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-30 @ 9:32 PM
Study NCT ID:
NCT07493161
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-25
First Post:
2026-03-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2026-03-25'}, 'interventionBrowseModule': {'meshes': [{'id': 'C579813', 'term': 'olverembatinib'}, {'id': 'C579720', 'term': 'venetoclax'}, {'id': 'C510808', 'term': 'blinatumomab'}, {'id': 'D016219', 'term': 'Immunotherapy, Adoptive'}], 'ancestors': [{'id': 'D019264', 'term': 'Adoptive Transfer'}, {'id': 'D007116', 'term': 'Immunization, Passive'}, {'id': 'D007114', 'term': 'Immunization'}, {'id': 'D007167', 'term': 'Immunotherapy'}, {'id': 'D056747', 'term': 'Immunomodulation'}, {'id': 'D001691', 'term': 'Biological Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D007158', 'term': 'Immunologic Techniques'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 100}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2026-04-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2026-03', 'completionDateStruct': {'date': '2030-03-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2026-03-19', 'studyFirstSubmitDate': '2026-03-19', 'studyFirstSubmitQcDate': '2026-03-19', 'lastUpdatePostDateStruct': {'date': '2026-03-25', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2026-03-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-03-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Rate of BCR::ABL1 ≤0.01% at 90 days (after three cycles of treatment)', 'timeFrame': 'up to 90 days'}, {'measure': 'Event-Free Survival', 'timeFrame': 'up to 5 years'}], 'secondaryOutcomes': [{'measure': 'Overall Survival', 'timeFrame': 'up to 5 years'}, {'measure': 'Relapse-Free Survival', 'timeFrame': 'up to 5 years'}, {'measure': 'Cumulative incidence of molecular relapse', 'timeFrame': 'up to 5 years'}, {'measure': 'Cumulative incidence of hematologic relapse', 'timeFrame': 'up to 5 years'}, {'measure': 'Proportion of patients with next-generation sequencing minimal residual disease <0.01% after three cycles of treatment (90 days)', 'timeFrame': 'up to 90 days'}, {'measure': 'Proportion of patients with next-generation sequencing minimal residual disease <0.01% at the end of consolidation therapy', 'timeFrame': 'up to 1 year'}, {'measure': 'Incidence of treatment-related cardiovascular events', 'timeFrame': 'up to 5 years from the initiation of treatment'}, {'measure': 'Proportion of patients with BCR::ABL1 ≤0.01% at completion of consolidation therapy', 'timeFrame': 'up to 90 days'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Ph+ ALL']}, 'descriptionModule': {'briefSummary': 'This is a prospective, open-label, randomized controlled trial to evaluate the efficacy and safety of low-intensity chemotherapy combined with targeted agents (venetoclax and blinatumomab) in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Patients will be randomized to receive or not receive venetoclax during the first three cycles of induction and consolidation therapy. All patients receive olverembatinib (a third-generation TKI) continuously and may receive up to 4 cycles of blinatumomab starting from the fourth cycle. The primary endpoint is the rate of BCR::ABL1 ≤0.01% at 90 days and event-free survival (EFS). Secondary endpoints include overall survival (OS), relapse-free survival (RFS), molecular relapse rate, MRD negativity rate by NGS, and cardiovascular events.', 'detailedDescription': 'Background: Ph+ ALL is a high-risk subtype of adult ALL. Although outcomes have improved with TKI-based therapy, achieving early deep molecular response remains critical for long-term survival. Novel combinations with BCL2 inhibitor venetoclax and CD3-CD19 bispecific antibody blinatumomab may further deepen responses.\n\nObjective: To determine whether adding venetoclax to a low-intensity chemotherapy backbone (vincristine, prednisone, olverembatinib) improves early molecular response and survival, and to explore the impact of different cycles of blinatumomab.\n\nDesign: This is a single-center, open-label, randomized controlled trial. Eligible patients are newly diagnosed Ph+ ALL aged ≥14 years, with ECOG ≤2 and adequate organ function. Patients will be randomized 1:1 to Arm A (control) or Arm B (venetoclax) during the first three cycles.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '14 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Newly diagnosed ALL with t(9;22)(q34;q11) or BCR::ABL1 positivity (by PCR or FISH).\n* Age ≥ 14 years.\n* ECOG performance status ≤ 2.\n* Adequate organ function: Total bilirubin \\<1.5x ULN; AST/ALT ≤2.5x ULN; Serum creatinine \\<2x ULN; Cardiac enzymes \\<2x ULN; Serum amylase ≤1.5x ULN; Left ventricular ejection fraction (LVEF) \\>45%.\n* Male and female patients of childbearing potential must agree to use effective contraception.\n* Signed informed consent.\n\nExclusion Criteria:\n\n* Diagnosis of chronic myeloid leukemia in chronic, accelerated, or blast phase.\n* Prior systemic anti-leukemic therapy for ALL (except corticosteroids or hydroxyurea for cytoreduction prior to enrollment).\n* Myocardial infarction within 12 months prior to enrollment; uncontrolled/unstable angina, congestive heart failure, uncontrolled hypertension or arrhythmia.\n* Uncontrolled active severe infection.\n* Active psychiatric illness that may hinder treatment completion or informed consent.\n* Any other condition deemed unsuitable for the study by the investigator.'}, 'identificationModule': {'nctId': 'NCT07493161', 'briefTitle': 'Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL', 'organization': {'class': 'OTHER', 'fullName': 'Institute of Hematology & Blood Diseases Hospital, China'}, 'officialTitle': 'Low-intensity Chemotherapy Combined With Targeted-Immunotherapy for Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Prospective Clinical Cohort Study', 'orgStudyIdInfo': {'id': 'IIT2026022'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Standard Therapy (Chemotherapy + Olverembatinib)', 'description': 'Patients receive a backbone of low-intensity chemotherapy combined with the third-generation TKI olverembatinib(OVB) .\n\nInduction : Vincristine D1,8,15,22; Prednisone D1-28; Olverembatinib (40mg every other day) D1-28；\n\nConsolidation 1 \\& 2: Olverembatinib D1-28; Prednisone D1-14；Vincristine D1,8. OVB dose is reduced to 20mg every other day for patients achieving CMR after Consolidation 1.\n\nSubsequent Chemotherapy: Includes High-Dose Methotrexate (cycles 4, 6, and 8 )and Intermediate-Dose Cytarabine( cycles 5, 7, and 9).\n\nMaintenance therapy:OVB maintenance therapy continues for at least 5 years.\n\nOptional Add-on: Patients with financial means may receive 1-4 cycles of blinatumomab, intercalated with chemotherapy starting after Consolidation 1.If the patient undergoes CAR-T therapy, the following conditioning regimen will be administered in cycle 4.\n\nAllogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.', 'interventionNames': ['Drug: Olverembatinib', 'Drug: Blinatumomab', 'Drug: Chemotherapy Backbone Regimens', 'Other: CAR-T Cell Therapy', 'Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)']}, {'type': 'EXPERIMENTAL', 'label': 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)', 'description': 'Patients receive the same backbone as the Control Arm plus the BCL2 inhibitor venetoclax (100mg D1,200 mg D2，400 mg D3-28) for the first three treatment blocks.\n\nConsolidation 1 \\& 2 (OP, 4 weeks each): Olverembatinib (40mg every other day) D1-28; Prednisone D1-14；Vincristine (VCR) D1,8. OVB dose is reduced to 20mg every other day for patients achieving CMR after Consolidation 1.\n\nSubsequent Chemotherapy: Includes High-Dose Methotrexate (cycles 4, 6, and 8 )and Intermediate-Dose Cytarabine( cycles 5, 7, and 9).\n\nMaintenance therapy:Olverembatinib maintenance therapy continues for at least 5 years.\n\nOptional Add-on: Patients with financial means may receive 1-4 cycles of blinatumomab, intercalated with chemotherapy starting after Consolidation 1.If the patient undergoes CAR-T therapy, the following conditioning regimen will be administered in cycle 4.\n\nAllogeneic HSCT is an option for patients with NGS MRD ≥0.01% after two cycles of treatment.', 'interventionNames': ['Drug: Olverembatinib', 'Drug: Venetoclax', 'Drug: Blinatumomab', 'Drug: Chemotherapy Backbone Regimens', 'Other: CAR-T Cell Therapy', 'Other: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)']}], 'interventions': [{'name': 'Olverembatinib', 'type': 'DRUG', 'description': 'Third-generation tyrosine kinase inhibitor (TKI) targeting BCR-ABL1, including T315I mutation.nduction \\& Consolidation: 40mg every other day.\n\nAfter achieving CMR: Reduced to 20mg every other day during maintenance.', 'armGroupLabels': ['Standard Therapy (Chemotherapy + Olverembatinib)', 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}, {'name': 'Venetoclax', 'type': 'DRUG', 'description': 'BCL-2 inhibitor. Used only in the experimental arm.Induction: Ramp-up: 100mg D1, 200mg D2, 400mg D3-28.\n\nConsolidation: 400mg D1-7.', 'armGroupLabels': ['Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}, {'name': 'Blinatumomab', 'type': 'DRUG', 'description': 'CD19/CD3 bispecific T-cell engager (BiTE). Optional add-on therapy.Start: After first consolidation.\n\nDuration: 1-4 cycles (each cycle = 28 days), intercalated with chemotherapy cycles.\n\nNote: If ≥3 cycles given,cycle 8 and 9 are omitted.', 'armGroupLabels': ['Standard Therapy (Chemotherapy + Olverembatinib)', 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}, {'name': 'Chemotherapy Backbone Regimens', 'type': 'DRUG', 'description': 'Induction (VPO/VPVO): Vincristine + Prednisone + Olverembatinib (± Venetoclax).\n\nConsolidation (VOVP/OVP): Vincristine +Olverembatinib + Prednisone (± Venetoclax).\n\nHD-MTX: High-dose methotrexate with leucovorin rescue in cycle 4,6,8.\n\nID-AraC: Intermediate-dose cytarabine in cycle 5,7,9.', 'armGroupLabels': ['Standard Therapy (Chemotherapy + Olverembatinib)', 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}, {'name': 'CAR-T Cell Therapy', 'type': 'OTHER', 'description': 'After second consolidation (optional pathway).', 'armGroupLabels': ['Standard Therapy (Chemotherapy + Olverembatinib)', 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}, {'name': 'Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)', 'type': 'OTHER', 'description': 'Recommended for patients with MRD ≥0.01% after two treatment blocks.', 'armGroupLabels': ['Standard Therapy (Chemotherapy + Olverembatinib)', 'Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Hui Wei, MD', 'role': 'CONTACT', 'email': 'weihui@ihcams.ac.cn', 'phone': '13132507161'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute of Hematology & Blood Diseases Hospital, China', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}