Immune-targeted Combination With Chemotherapy for Acute Leukemia of Ambiguous Lineage

Immune-targeted Combination With Acute Lymphoblastic Leukemia-like Chemotherapy for Adult of Acute Leukemia of Ambiguous Lineage: A Prospective, Single-arm, Multicenter Clinical Study

Acute leukemia of ambiguous lineage (ALAL), which refers to acute leukemia without definite evidence indicating cell differentiation along a specific lineage, mainly encompasses two major categories: acute undifferentiated leukemia (AUL) lacking the expression of lineage-specific antigens and mixed phenotype acute leukemia (MPAL) expressing antigens of two or more lineages. Despite certain advancements in basic research on ALAL, there is currently no unified treatment protocol for this disease. The majority of clinical studies are based on retrospective data, lacking prospective cohort studies. In terms of the overall treatment strategy, given the low chemotherapy remission rate, frequent relapses, and poor prognosis of ALAL, it should be treated as high-risk acute leukemia. Patients achieving complete remission should undergo allogeneic hematopoietic stem cell transplantation as soon as possible if conditions permit. Regarding chemotherapy regimens, the current main regimens utilized in clinical practice include ALL-like regimens, AML-like regimens, and hybrid therapies that incorporate both lymphoid and myeloid lineages. Based on existing research, international consensus guidelines recommend ALL-like regimens as the preferred induction treatment option for ALAL patients. In recent years, novel immunotherapy antibody drugs, such as Blinatumomab (a CD19-targeted drug), have achieved remarkable success in the treatment of B-ALL. However, for CD19+ ALAL, there is a lack of effective data regarding whether the first-line application of immunotherapy can further enhance therapeutic efficacy. Simultaneously, the novel small molecule drug venetoclax has demonstrated favorable therapeutic effects on various hematological malignancies. To enhance the overall therapeutic efficacy of adult ALAL in China, based on the above research, we have formulated a comprehensive treatment plan for adult ALAL, integrating Blinatumomab, ALL-like chemotherapy, venetoclax, and TKI drugs into the systemic treatment regimen, and exploring the safety and efficacy of this regimen in the treatment of adult ALAL.

Study Overview

• Status: Not yet recruiting
• Conditions: Adult ALL; MPAL
• Intervention / Treatment: Drug: Blinatumomab; Drug: Venetoclax

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hui Wei, MD; Phone Number: 13132507161; Email: weihui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• A series of acute leukemia of unknown origin diagnosed in accordance with the 5th edition of the WHO or ICC classification standards.
• Age ≥ 14 years old, regardless of gender.
• The ECOG performance status score is ≤ 2.
• Conform to the following organ functional status: total bilirubin < 1.5×ULN, AST and ALT ≤ 2.5×ULN; blood Cr < 1.5×ULN; myocardial enzymes < 2×ULN; serum amylase ≤ 1.5×ULN; echocardiography indicates that the left ventricular ejection fraction (LEF) > 50%. (In the case of patients without a previous history of liver or kidney basic disease, if liver and kidney function abnormalities exceed the aforementioned inclusion criteria and the researcher determines that the liver and kidney function abnormalities are caused by acute leukemia itself, they may be included in the group at the researcher's discretion).
• Understand and sign the informed consent form and agree to abide by the research requirements.

Exclusion Criteria:

• Concurrent with other serious and/or uncontrollable underlying diseases: accompanied by other malignant diseases requiring treatment, acute or chronic hepatitis, severe pancreatic or kidney diseases; other serious and/or life-threatening underlying diseases.
• Pregnant or lactating women.
• Positive for anti-HIV test.
• Mental disorders that may prevent the subject from completing the treatment or giving informed consent.
• The investigator deems the subject unsuitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Systematic treatment strategy; Integrate Blinatumomab, ALL-like chemotherapy, Venetoclax and TKI drugs into the systemic treatment plan

Drug: Blinatumomab; CD19-positive, Ph+ patients with favorable financial status may receive VP + TKI + blinatumomab therapy；CD19-positive, Ph- patients with favorable financial status may receive VCP + blinatumomab therapy.; Drug: Venetoclax; CD19-positive, Ph+ patients with poor financial status may receive VP + TKI + VEN therapy；CD19-negative or CD19-positive, Ph- patients ineligible for blinatumomab may receive VPCLP + VEN therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	Used to evaluate all patients who enter clinical trials. From the date of entry into the trial until the date of patient death (including any cause) or last survival follow-up.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	The interval from the date of enrollment to the date of failed to achieve complete remission, the date of relapse, or the date of death, whichever occurred first.	up to 2 years after the date of the last enrolled participants
Complete remission (CR) rate or complete remission with partial hematologic recovery (CRh) rate or complete remission with incomplete hematologic recovery (CRi) rate	Proportion of patients with CR, CRh or Cri	Six weeks after induction therapy
Flow cytometry for minimal residual disease（FCM-MRD） negativity rate at 3 months post-therapy	FCM-MRD is a method that detects residual trace leukemia or lymphoma cells in patients' bodies after treatment	3 months after therapy
Relapse free survival(RFS)	The interval from CR to the date of relapse, or the date of death, or the date of last follow-up, whichever occurred first. This outcome analyzes patients achieved CR in two courses of induction therapy.	up to 2 years after the date of the last enrolled participants
Disease-free Survival (DFS)	From CR1 to relapse, death from any cause or last follow-up	up to 2 years after the date of the last enrolled participants

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Hui Wei, MD, Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: March 17, 2025
• First Submitted That Met QC Criteria: May 26, 2025
• First Posted (Actual): May 28, 2025

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Antineoplastic Agents; venetoclax; blinatumomab
• Other Study ID Numbers: IIT2024114

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No