Trial Title:
Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Elderly/Unfit Ph- B-ALL
NCT ID:
NCT06387121
Condition:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Methotrexate
Vincristine
Venetoclax
Mercaptopurine
Blinatumomab
Inotuzumab Ozogamicin
Conditions: Keywords:
Philadelphia Chromosome-Negative
Acute Lymphoblastic Leukemia
Elderly Or Unfit
Immuno-targeted Drugs
Low-dose Chemotherapy
Single-arm Clinical Study
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Anti-tumor alkaloids
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
VCR
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Alkylating agent
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
CTX
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Glucocorticoids
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
DEX
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Selective inhibitor of B-cell lymphoma 2 (Bcl-2)
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
VEN
Intervention type:
Drug
Intervention name:
Inotuzumab ozogamicin
Description:
A humanized monoclonal antibody-drug conjugate targeting CD22
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
INO
Intervention type:
Drug
Intervention name:
Blinatumomab
Description:
Bi-specific anti-CD19/CD3 antibodies
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
Blino
Intervention type:
Drug
Intervention name:
6-mercaptopurine
Description:
Cell cycle-specific antitumor drug
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
6-MP
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Antifolate antineoplastic drug
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
MTX
Intervention type:
Drug
Intervention name:
Cytarabine
Description:
Pyrimidine antimetabolites
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
Ara-C
Intervention type:
Drug
Intervention name:
Prednisone
Description:
Glucocorticoids
Arm group label:
low-dose chemotherapy combined with Venetoclax
Arm group label:
low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs
Other name:
Pred
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.
Criteria for eligibility:
Criteria:
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. ≥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
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
April 15, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06387121
