Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Elderly/Unfit Ph- B-ALL
- Conditions
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Interventions
- Registration Number
- NCT06387121
- Brief Summary
In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL), despite the achievements of chemotherapy and immunotherapy, the therapeutic outcomes are unsatisfactory in elderly or unfit patients. In recent years, tumor immunotherapy has demonstrated a high safety and efficacy profile in refractory Ph- B-ALL patients. These findings suggest that the advancement of immunotherapy application may be an important approach to improve patient survival. In this study, we propose a treatment approach that combines immuno-targeted drugs with low-dose chemotherapy for newly diagnosed elderly or unfit patients with Ph- B-ALL, aiming to enhance the measurable residual disease (MRD)-negative complete remission (CR) rate measured through flow cytometry following induction therapy, reduce the risk of relapse, and ultimately improve patients' overall survival.
- Detailed Description
In this open-label, single-arm, Phase II study, prospective clinical trial, a total of 53 Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) patients will be enrolled. The primary endpoint is measurable residual disease (MRD)-negative complete remission (CR) rate after induction therapy.
The first cycle of induction therapy is administered with Inotuzumab ozogamicin (INO), Venetoclax (VEN), and a combination of low-dose chemotherapy. The second cycle of induction therapy is Blinatumomab (Blino) plus VEN regimen. Alternatively, the first cycle of induction therapy is a combination of VEN and low-dose chemotherapy, and the second cycle of induction therapy is methotrexate (MTX) plus cytarabine (Ara-C) plus VEN regimen. Subsequent consolidation and maintenance therapy consist of low-dose chemotherapy, Blino, and VEN. Patients can receive chimeric antigen receptor T-Cell (CAR-T) Immunotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) or receive autologous HSCT whenever possible during their first CR. Otherwise, they will finish the consolidation chemotherapy. Study patients are scheduled for follow-up for at least 5 years after the end of maintenance therapy.
The purpose of current study is to determine the efficacy and safety of low-dose chemotherapy combined with immuno-targeted drugs in newly diagnosed elderly or unfit patients with Ph- B-ALL.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 53
- Newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia according to World Health Organization (WHO) 2016 criteria
- CD22 positive tumor cells
- ≥60 years of age, or 18 to 59 years of age, with at least one of the following: Eastern Cooperative Oncology Group (ECOG) performance status of 2 - 3; severe heart, lung, liver, or kidney disease; presence of comorbidities that are not suitable for intensive chemotherapy in the physician's judgment
- Estimated survival ≥3 months
- Consent and effective contraception for men and women of childbearing potential
- Understanding and signing of informed consent forms and agreement to comply with study requirements.
- Burkitt lymphoma/leukemia
- acute leukemias of ambiguous lineage
- pregnant women
- severe uncontrolled active infection
- previous history of chronic liver disease (e.g. cirrhosis) or venous occlusive liver disease (VOD) or sinus obstruction syndrome (SOS)
- History of clinically significant ventricular arrhythmia, syncope of unknown origin (not vasovagal) or sinoatrial block or higher degree atrioventricular (AV) block Chronic bradycardia state (unless permanent pacemaker implanted)
- New or chronic hepatitis B or C infection (positive for hepatitis B surface antigen and anti-hepatitis C antibody, respectively) or known HIV seropositivity. HIV testing may need to be performed according to local regulations or practices
- Psychiatric disorders likely to prevent the subject from completing treatment or informed consent
- Other conditions considered unsuitable for the study by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Vincristine The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Venetoclax The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Inotuzumab ozogamicin The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Blinatumomab The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Methotrexate The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Cytarabine The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Prednisone The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy combined with Venetoclax Vincristine The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Cyclophosphamide The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Dexamethasone The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Venetoclax The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax 6-mercaptopurine The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Methotrexate The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Cytarabine The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy combined with Venetoclax Prednisone The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN. low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Dexamethasone The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs Cyclophosphamide The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN). low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs 6-mercaptopurine The cycle of induction therapy is administered with immuno-targeted drugs (including Inotuzumab ozogamicin and/or Blinatumomab), a combination of low-dose chemotherapy (including vincristine, cyclophosphamide, dexamethasone, methotrexate and cytarabine) and Venetoclax (VEN).
- Primary Outcome Measures
Name Time Method MRD-negative complete remission rate measured by flow cytometry. After induction (4 week) No immature cells were detected by flow cytometry when CR criteria were met after induction therapy.
- Secondary Outcome Measures
Name Time Method Mortality Day 30 and Day 60 of induction therapy initiation Complete remission (CR) rate an expected average of 3 months Overall survival (OS) Up to 5 years post-registration From the date of registration to the date of death resulting from any cause.
Relapse free survival (RFS) Up to 5 years post-registration From the date of complete remission (CR) until the date of documented relapse or death due to any cause or last follow-up.
Disease-free Survival (DFS) Up to 5 years post-registration From CR1 to relapse, death from any cause or last follow-up.
Trial Locations
- Locations (1)
Institute of Hematology & Blood Diseases Hospital
🇨🇳Tianjin, Tianjin, China