Efficacy and Safety of Low-dose Chemotherapy Plus Immuno-targeted Drugs in Newly Diagnosed Adult Ph- B-ALL

NCT ID: NCT06387121

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-02

Study Completion Date

2028-12-31

Brief Summary

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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

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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.

Conditions

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Precursor Cell Lymphoblastic Leukemia-Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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low-dose chemotherapy, Venetoclax combined with immuno-targeted drugs

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).

Group Type EXPERIMENTAL

Vincristine

Intervention Type DRUG

Anti-tumor alkaloids

Cyclophosphamide

Intervention Type DRUG

Alkylating agent

Dexamethasone

Intervention Type DRUG

Glucocorticoids

Venetoclax

Intervention Type DRUG

Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Inotuzumab ozogamicin

Intervention Type DRUG

A humanized monoclonal antibody-drug conjugate targeting CD22

Blinatumomab

Intervention Type DRUG

Bi-specific anti-CD19/CD3 antibodies

6-mercaptopurine

Intervention Type DRUG

Cell cycle-specific antitumor drug

Methotrexate

Intervention Type DRUG

Antifolate antineoplastic drug

Cytarabine

Intervention Type DRUG

Pyrimidine antimetabolites

Prednisone

Intervention Type DRUG

Glucocorticoids

low-dose chemotherapy combined with Venetoclax

The cycle of induction therapy is administered with a combination of low-dose chemotherapy and VEN.

Group Type EXPERIMENTAL

Vincristine

Intervention Type DRUG

Anti-tumor alkaloids

Cyclophosphamide

Intervention Type DRUG

Alkylating agent

Dexamethasone

Intervention Type DRUG

Glucocorticoids

Venetoclax

Intervention Type DRUG

Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

6-mercaptopurine

Intervention Type DRUG

Cell cycle-specific antitumor drug

Methotrexate

Intervention Type DRUG

Antifolate antineoplastic drug

Cytarabine

Intervention Type DRUG

Pyrimidine antimetabolites

Prednisone

Intervention Type DRUG

Glucocorticoids

Interventions

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Vincristine

Anti-tumor alkaloids

Intervention Type DRUG

Cyclophosphamide

Alkylating agent

Intervention Type DRUG

Dexamethasone

Glucocorticoids

Intervention Type DRUG

Venetoclax

Selective inhibitor of B-cell lymphoma 2 (Bcl-2)

Intervention Type DRUG

Inotuzumab ozogamicin

A humanized monoclonal antibody-drug conjugate targeting CD22

Intervention Type DRUG

Blinatumomab

Bi-specific anti-CD19/CD3 antibodies

Intervention Type DRUG

6-mercaptopurine

Cell cycle-specific antitumor drug

Intervention Type DRUG

Methotrexate

Antifolate antineoplastic drug

Intervention Type DRUG

Cytarabine

Pyrimidine antimetabolites

Intervention Type DRUG

Prednisone

Glucocorticoids

Intervention Type DRUG

Other Intervention Names

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VCR CTX DEX VEN INO Blino 6-MP MTX Ara-C Pred

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jianxiang Wang

Role: PRINCIPAL_INVESTIGATOR

Institute of Hematology & Blood Diseases Hospital, China

Locations

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Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jianxiang Wang

Role: CONTACT

+862223909120

Facility Contacts

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Wang Jianxiang

Role: primary

022-23909120

References

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Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017 Jun 30;7(6):e577. doi: 10.1038/bcj.2017.53.

Reference Type BACKGROUND
PMID: 28665419 (View on PubMed)

Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB, Schmiegelow K, Escherich G, Horibe K, Benoit YC, Izraeli S, Yeoh AE, Liang DC, Downing JR, Evans WE, Relling MV, Mullighan CG. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):2938-48. doi: 10.1200/JCO.2014.59.1636. Epub 2015 Aug 24.

Reference Type BACKGROUND
PMID: 26304874 (View on PubMed)

Boissel N, Auclerc MF, Lheritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, Piguet C, Huguet-Rigal F, Berthou C, Boiron JM, Pautas C, Michel G, Fiere D, Leverger G, Dombret H, Baruchel A. Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol. 2003 Mar 1;21(5):774-80. doi: 10.1200/JCO.2003.02.053. Epub 2003 Mar 1.

Reference Type BACKGROUND
PMID: 12610173 (View on PubMed)

O'Brien S, Thomas DA, Ravandi F, Faderl S, Pierce S, Kantarjian H. Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer. 2008 Oct 15;113(8):2097-101. doi: 10.1002/cncr.23819.

Reference Type BACKGROUND
PMID: 18720356 (View on PubMed)

Geyer MB, Hsu M, Devlin SM, Tallman MS, Douer D, Park JH. Overall survival among older US adults with ALL remains low despite modest improvement since 1980: SEER analysis. Blood. 2017 Mar 30;129(13):1878-1881. doi: 10.1182/blood-2016-11-749507. Epub 2017 Jan 25. No abstract available.

Reference Type BACKGROUND
PMID: 28122741 (View on PubMed)

Maury S, Chevret S, Thomas X, Heim D, Leguay T, Huguet F, Chevallier P, Hunault M, Boissel N, Escoffre-Barbe M, Hess U, Vey N, Pignon JM, Braun T, Marolleau JP, Cahn JY, Chalandon Y, Lheritier V, Beldjord K, Bene MC, Ifrah N, Dombret H; for GRAALL. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Sep 15;375(11):1044-53. doi: 10.1056/NEJMoa1605085.

Reference Type BACKGROUND
PMID: 27626518 (View on PubMed)

Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bruggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017 Mar 2;376(9):836-847. doi: 10.1056/NEJMoa1609783.

Reference Type BACKGROUND
PMID: 28249141 (View on PubMed)

Other Identifiers

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IIT2023060

Identifier Type: -

Identifier Source: org_study_id