Modified TBF Regimen as Conditioning Regimen Prior to Allo-HSCT for T-ALL/LBL

NCT05598593 | Unknown Phase 2 DMC

• 1 other identifier: ZJU-HSCT-MTBF
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

T cell acute lymphoblastic leukemia (T-ALL)/Lymphoblastic lymphoma (LBL) is a hematological malignancy caused by malignant transformation and clonal expansion of T-lineage precursor cells. The long-term cure rate of pediatric patients with T-ALL/LBL reaches 90%, but long-term survival of adult patients is less than 60%. Moreover, patients with high-risk factors such as PTEN/NRAS gene mutation, early T cell precursor (ETP) phenotype or positive minimal residual disease (MRD) have high rates of chemoresistance and dismal outcome. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can significantly improve the prognosis of high-risk T-ALL/LBL. Total body irradiation (TBI)-based conditioning chemotherapy regimen is the preferred regimen for allo-HSCT in children and young adults with ALL because of lower relapse rates and satisfactory survival. Different from children, the non-relapse-related mortality (NRM) after TBI-based preconditioning in adults (especially those \>35 years old) was reported as high as 38%. In addition, serious sequelae after TBI seriously affect the quality of life and non-radiation conditioning chemotherapy regimens are urgently needed for T-ALL/LBL. The reported recurrence rates after BUCY (busulfan + cyclophosphamide) conditioning regimen for T-ALL as 41.2%. -56.7% and long-term survival was only 30-50%. Thiotepa is an ethyleneimine alkylating agent with anti-tumor effects and immunosuppressive effects, thus is widely used in conditioning regimen before HSCT. Retrospective paired analysis from EBMT indicated conditioning regimen thiotepa achieved similar relapse rates, long-term survival and faster granulocyte and platelet engraftment than TBI regimen. A recent retrospective study of childhood ALL from Turkey also reported that the TBF(thiotepa + fludarabine + busulfan) regimen had a recurrence rate of only 11.9% , a non-relapse mortality rate of 14.0% and a long-term survival of 79.1%. Data from a large retrospective paired study suggested TBF regimen can significantly reduce the relapse rate of acute myeloid leukemia after the first remission (HR=0.4, CI 0.2-0.7, P = .02) without increasing treatment related deaths compared with the traditional BUCY regimen. Based on these data, we modified the TBF regimen with additional cytarabine for allo-HSCT in T-ALL/LBL with expection to reduced disease relapse and improved long-term survival.

Conditions

Cytarabine+Thiotepa + Fludarabine + Busulfan; T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

Keywords

allogeneic hematopoietic stem cell transplantation; T cell Acute Lymphoblastic Leukemia/Lymphoblastic lymphoma; thiotepa

Outcome Measures

Primary Outcomes (1)

• Disease free survival

  2-year DFS

  2 year

Secondary Outcomes (4)

• incidence of toxic reaction

  2 year

• overall survival

  2 year

• umulative incidence of relapse

  2 year

• ncidence of acute and or chronic graft verus host disease

  2 year

Study Arms (1)

Modified TBF Conditioning Regimen

EXPERIMENTAL

thiotepa 5mg/kg/d d-9 to d-8, cytarabine 0-4.0 g/m2/d d-7 to d-6(adjusted according to patients' age and HCT-CI index), fludarabine 30mg/m2/d d-7 to d-3, busulfan 3.2mg/m2/d d-5 to d-3

Drug: cytarabine+thiotepa+ fludarabine + busulfan

Interventions

cytarabine+thiotepa+ fludarabine + busulfan DRUG

cytarabine+thiotepa+ fludarabine + busulfan intravenous injection

Modified TBF Conditioning Regimen

Eligibility Criteria

• Age: 4 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age younger than 65 years
• Patients diagnosed with T cell acute lymphoblastic leukemia/lymphoma , T-ALL/LBL according to WHO diagnostic criteria.
• Patients who have donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
• ECOG body status score 0-2.
• Good organ function level: ANC (neutrophil absolute value \>=1.0x10\^9/ L; PLT \>=30x10\^9/L; HB \>=80g/L; Tibil \<=1.5 ULN; ALT / AST \<=2.5 ULN; bun / Cr \<=1.5 ULN; LVEF \>=50%).
• Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.

You may not qualify if:

• Patients who with severe cardiac insufficiency, cardiac ejection fraction EF is less than 60%; or severe arrhythmia, the investigator can not tolerate conditioning chemotherapy;
• In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate conditioning chemotherapy;
• Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of conditioning chemotherapy;
• In patients with severe renal insufficiency, the renal function index (CR) is more than 2 times of the upper limit of the normal value (ULN), or the 24-hour creatinine clearance rate (CR) is less than 50ml / min, the researchers evaluated that they could not tolerate conditioning chemotherapy;
• In patients with severe active infection, the researchers evaluated that they could not tolerate conditioning chemotherapy;
• Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
• Other reasons why the researchers could not be selected.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Busulfan

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)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Yi Luo, M.D.

  First Affilaated Hospital of Medical School of Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yi Luo, M.D.

CONTACT

+86057187233801; luoyijr@163.com

Luxin Yang, M.D.

CONTACT

+86057187233772; yangluxin2016@126.com

Study Design

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

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: October 28, 2022
• Study Start: October 23, 2022
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2025
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)