Chemotherapy With Targeted-Immunotherapy for Newly Diagnosed Ph+ ALL
ConditionPh+ ALL
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age14+
SponsorInstitute of Hematology & Blood Diseases Hospital, China
About this trial
This is a prospective, open-label, randomized controlled trial to evaluate the efficacy of low-intensity chemotherapy combined with 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Newly diagnosed ALL with t(9;22)(q34;q11) or BCR::ABL1 positivity (by PCR or FISH).
Age ≥ 14 years.
ECOG performance status ≤ 2.
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%.
Disqualifiers
Diagnosis of chronic myeloid leukemia in chronic, accelerated, or blast phase.
Prior systemic anti-leukemic therapy for ALL (except corticosteroids or hydroxyurea for cytoreduction prior to enrollment).
Myocardial infarction within 12 months prior to enrollment; uncontrolled/unstable angina, congestive heart failure, uncontrolled hypertension or arrhythmia.
Uncontrolled active severe infection.
Trial design
Design model
Parallel
Treatments tested in this trial
Olverembatinib
DrugThird-generation tyrosine kinase inhibitor (TKI) targeting BCR-ABL1, including T315I mutation.nduction \& Consolidation: 40mg every other day. After achieving CMR: Reduced to 20mg every other day during maintenance.
Venetoclax
DrugBCL-2 inhibitor. Used only in the experimental arm.Induction: Ramp-up: 100mg D1, 200mg D2, 400mg D3-28. Consolidation: 400mg D1-7.
Blinatumomab
DrugCD19/CD3 bispecific T-cell engager (BiTE). Optional add-on therapy.Start: After first consolidation. Duration: 1-4 cycles (each cycle = 28 days), intercalated with chemotherapy cycles. Note: If ≥3 cycles given,cycle 8 and 9 are omitted.
Chemotherapy Backbone Regimens
DrugInduction (VPO/VPVO): Vincristine + Prednisone + Olverembatinib (± Venetoclax). Consolidation (VOVP/OVP): Vincristine +Olverembatinib + Prednisone (± Venetoclax). HD-MTX: High-dose methotrexate with leucovorin rescue in cycle 4,6,8. ID-AraC: Intermediate-dose cytarabine in cycle 5,7,9.
Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
Other interventionRecommended for patients with MRD ≥0.01% after two treatment blocks.
Treatment groups
110 Participants
are divided into 2 treatment groupsGroup A: Standard Therapy (Chemotherapy + Olverembatinib)Active comparator 4 interventions
Group B: Venetoclax-Added Therapy (Chemotherapy + Olverembatinib + Venetoclax)Experimental treatment 5 interventions
Trial outcomes
Primary outcomes
1
Rate of BCR::ABL1 ≤0.01% at 90 days (after three cycles of treatment)
Time frame
up to 90 days2
Event-Free Survival
Time frame
up to 5 yearsSecondary outcomes
1
Overall Survival
Time frame
up to 5 years2
Relapse-Free Survival
Time frame
up to 5 years3
Cumulative incidence of molecular relapse
Time frame
up to 5 years4
Cumulative incidence of hematologic relapse
Time frame
up to 5 yearsSponsors and contacts
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Source ClinicalTrials.gov