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

NCT06387121 | Recruiting Phase 2

• 1 other identifier: IIT2023060
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Keywords

Philadelphia Chromosome-Negative; Acute Lymphoblastic Leukemia; Elderly Or Unfit; Immuno-targeted Drugs; Low-dose Chemotherapy; Single-arm Clinical Study

Outcome Measures

Primary Outcomes (1)

• MRD-negative complete remission rate measured by flow cytometry.

  No immature cells were detected by flow cytometry when CR criteria were met after induction therapy.

  After induction (4 week)

Secondary Outcomes (5)

• Complete remission (CR) rate

  an expected average of 3 months

• Overall survival (OS)

  Up to 5 years post-registration

• Relapse free survival (RFS)

  Up to 5 years post-registration

• Disease-free Survival (DFS)

  Up to 5 years post-registration

• Mortality

  Day 30 and Day 60 of induction therapy initiation

Study Arms (2)

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

EXPERIMENTAL

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).

Drug: Vincristine; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Venetoclax; Drug: Inotuzumab ozogamicin; Drug: Blinatumomab; Drug: 6-mercaptopurine; Drug: Methotrexate; Drug: Cytarabine; Drug: Prednisone

low-dose chemotherapy combined with Venetoclax

EXPERIMENTAL

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

Drug: Vincristine; Drug: Cyclophosphamide; Drug: Dexamethasone; Drug: Venetoclax; Drug: 6-mercaptopurine; Drug: Methotrexate; Drug: Cytarabine; Drug: Prednisone

Interventions

Vincristine DRUG

Anti-tumor alkaloids

Also known as: VCR

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

Cyclophosphamide DRUG

Alkylating agent

Also known as: CTX

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

Dexamethasone DRUG

Glucocorticoids

Also known as: DEX

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

Venetoclax DRUG

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

Also known as: VEN

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

Inotuzumab ozogamicin DRUG

A humanized monoclonal antibody-drug conjugate targeting CD22

Also known as: INO

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

Blinatumomab DRUG

Bi-specific anti-CD19/CD3 antibodies

Also known as: Blino

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

6-mercaptopurine DRUG

Cell cycle-specific antitumor drug

Also known as: 6-MP

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

Methotrexate DRUG

Antifolate antineoplastic drug

Also known as: MTX

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

Cytarabine DRUG

Pyrimidine antimetabolites

Also known as: Ara-C

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

Prednisone DRUG

Glucocorticoids

Also known as: Pred

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia according to World Health Organization (WHO) 2016 criteria
• CD22 positive tumor cells
• ≥18 years of age
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital

Tianjin, Tianjin Municipality, China

RECRUITING

Related Publications (7)

• 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.

  PMID: 28665419 BACKGROUND

• 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.

  PMID: 26304874 BACKGROUND

• 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.

  PMID: 12610173 BACKGROUND

• 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.

  PMID: 18720356 BACKGROUND

• 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.

  PMID: 28122741 BACKGROUND

• 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.

  PMID: 27626518 BACKGROUND

• 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.

  PMID: 28249141 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Vincristine; Cyclophosphamide; Dexamethasone; venetoclax; Inotuzumab Ozogamicin; blinatumomab; Mercaptopurine; Methotrexate; Cytarabine; Prednisone; prednylidene

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfhydryl Compounds; Sulfur Compounds; Purines; Aminopterin; Pterins; Pteridines; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienediols

Study Officials

• Jianxiang Wang

  Institute of Hematology & Blood Diseases Hospital, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxiang Wang

CONTACT

+862223909120; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: April 26, 2024
• Study Start: April 2, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 17, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)