Venetoclax Plus IM2 Regimen for Relapsed and Refractory T Lymphoblastic Lymphoma/Leukemia

The Efficacy and Safety of Venetoclax Plus IM2 Regimen for Relapsed and Refractory T Lymphoblastic Lymphoma/Leukemia

To evaluate the safety and efficacy of Venetoclax plus IM2 regimen for relapsed and refractory T lymphoblastic lymphoma/leukemia. Dosage of Venetoclax:100mg/d-400mg/d(dose adjustment when concomitant used with CYP3A inhibitor) for 1-28 days (at least 7 days); IM2 regimen: Ifosfamide 1-1.5g/m2/d for 5 days; Mitoxantrone 6-8g/m2/d for 3 days( or Liposome mitoxantrone 20mg/m2 d1 or Idarubicin 6-8mg/m2/d for 3 days) ;methotrexate 1-1.5g/m2/d for 1 day;

Study Overview

• Status: Recruiting
• Conditions: Refractory Lymphoma; Refractory Leukemia; Efficacy, Self; T-lymphoblastic Lymphoma; Safety; Relapsed Disease
• Intervention / Treatment: Drug: BCL2 Inhibitor plus IM2 regimen

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xianmin G Song; Phone Number: +862163240090; Email: shongxm@139.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai General hospital,Shanghai Jiao Tong University School of Medicine
      • Contact: Xianmin G Song; Phone Number: +862163240090; Email: shongxm@139.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Fourteen to 45 Years Old, Male and female; Expected survival > 12 weeks; ECOG score 0-2; Confirmed diagnosis of T lymphoblastic lymphoma： a. Patients who do not get a PR with ≥2 induction chemotherapy or a CR with ≥ 4 induction chemotherapy b. Relapsed patients c. For any Patients who failed ASCT/allo-SCT d.The disease can be assessed (BM or CT scan) Confirmed diagnosis of acute T lymphoblastic leukemia (disease involved in BM, and no signs of lymph nodes or mass involvement): Patients who do not get a CR with ≥2 prior induction therapy such as Hyper-A and B regimens. b. relapsed after CR with chemotherapy c. For any Patients failed ASCT/allo-SCT Liver, kidney, and cardiopulmonary functions meet the following requirements: a. Ccr≥60mL/min(Cockcroft Gault) b. Left ventricular ejection fraction >50%; c.Baseline oxygen saturation>92%; d. Total bilirubin ≤ 1.5×ULN; e. ALT and AST≤ 3×ULN; Able to understand and sign the Informed Consent

Exclusion Criteria:

Malignant tumors other than T cell malignancies within 5 years prior to screening, in addition, to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection; Uncontrolled infection including bacterial or virus or fungal disease; patients with positive HBsAg or HBcAb and positive peripheral blood HBV DNA titer detection; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; syphilis positive; Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease; Any uncontrolled disease may affect entry Current or history of CNS involvement by malignancy.Known history or presence of clinically relevant central nervous system (CNS) pathology.Patients with a known history or prior diagnosis of other immunologic or inflammatory disease affecting the CNS (such as epilepsy) Pregnant or lactating woman, and a female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; Active or uncontrollable infection requiring systemic therapy Known be allergic to Venetoclax or Ifosfamide or Mitoxantrone or Idarubicin or methotrexate The investigators consider other conditions unsuitable for enrollment. Early relapse(time from the end of IM2 regimen to relapse within 6 months ) post- or refractory to IM2 chemotherapy Patients who may not be able to sign the Informed Consent due to disease,or who do not understand or unwillingness or inability to comply with research requirements

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: bcl-2 inhibitor plus IM2 regimen	Drug: BCL2 Inhibitor plus IM2 regimen; oral bcl-2 inhibitor plus IM2(Ifosfamide plus Mitoxantrone or Idarubicin plus methotrexate) chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate after 2 cycles of chemotherapy	complete response rate plus partial response rate	2 months after chemotherapy
Overall response rate after 4 cycles of chemotherapy	complete response rate plus partial response rate	4 months after chemotherapy
Grade 3-4 Adverse events incidence	Grade 3-4 Adverse events incidence	28 days after chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	OS for patients enrolled	12 months
Progression free survival	PFS for patients enrolled	12 months

Collaborators and Investigators

• Sponsor: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
• Investigators: Principal Investigator: Xianmin G Song, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2023
• Primary Completion (Estimated): October 10, 2024
• Study Completion (Estimated): October 10, 2025

Study Registration Dates

• First Submitted: October 9, 2022
• First Submitted That Met QC Criteria: October 9, 2022
• First Posted (Actual): October 12, 2022

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Other Study ID Numbers: SHXYXY-2022-VEN-T-LBL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No