Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions
Keywords
Philadelphia Chromosome-Negative, Acute Lymphoblastic Leukemia, Elderly Or Unfit, Immuno-targeted Drugs, Low-dose Chemotherapy, Single-arm Clinical Study
Brief summary
In the treatment of Ph-negative (Ph-) B-cell acute lymphoblastic leukemia (B-ALL) among adult patients, therapeutic outcomes remain suboptimal despite advances in chemotherapy and immunotherapy. A subset of adults with Ph- B-ALL have comorbidities or physiological limitations that preclude the safe administration of intensive regimens. In recent years, tumor immunotherapy has demonstrated promising safety and efficacy profiles in refractory or relapsed Ph- B-ALL across a wide spectrum of adult ages. These findings suggest that broader application of immunotherapy may represent a critical strategy to improve survival in this population. In this study, we propose a regimen that combines immuno-targeted agents with low-intensity chemotherapy for newly diagnosed adult patients with Ph- B-ALL. Our primary objective is to increase the rate of measurable residual disease (MRD)-negative complete remission (CR) following induction therapy, reduce the risk of relapse, and ultimately enhance 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 adult patients with Ph- B-ALL.
Interventions
DRUGVincristine
Anti-tumor alkaloids
DRUGCyclophosphamide
Alkylating agent
DRUGDexamethasone
Glucocorticoids
DRUGVenetoclax
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
DRUGInotuzumab ozogamicin
A humanized monoclonal antibody-drug conjugate targeting CD22
DRUGBlinatumomab
Bi-specific anti-CD19/CD3 antibodies
DRUG6-mercaptopurine
Cell cycle-specific antitumor drug
DRUGMethotrexate
Antifolate antineoplastic drug
DRUGCytarabine
Pyrimidine antimetabolites
DRUGPrednisone
Glucocorticoids
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia according to World Health Organization (WHO) 2016 criteria 2. CD22 positive tumor cells 3. ≥18 years of age 4. Estimated survival ≥3 months 5. Consent and effective contraception for men and women of childbearing potential 6. Understanding and signing of informed consent forms and agreement to comply with study requirements.
Exclusion criteria
1. Burkitt lymphoma/leukemia 2. acute leukemias of ambiguous lineage 3. pregnant women 4. severe uncontrolled active infection 5. previous history of chronic liver disease (e.g. cirrhosis) or venous occlusive liver disease (VOD) or sinus obstruction syndrome (SOS) 6. 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) 7. 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 8. Psychiatric disorders likely to prevent the subject from completing treatment or informed consent 9. Other conditions considered unsuitable for the study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Mortality | Day 30 and Day 60 of induction therapy initiation | — |
Countries
China
Contacts
Primary ContactJianxiang Wang
Outcome results
None listed