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

October 26, 2022 updated by: First Affiliated Hospital of Zhejiang University

Modified TBF Regimen as Conditioning Regimen Prior to Allogeneic Hematopoietic Cell Transplantation for T Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma：Phase II Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Hangzhou, China
        • Recruiting
        • The First Affiliated Hospital, College of Medicine, Zhejiang University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age younger than 65 years
  2. Patients diagnosed with T cell acute lymphoblastic leukemia/lymphoma , T-ALL/LBL according to WHO diagnostic criteria.
  3. Patients who have donors and plane to accept allogeneic hematopoietic stem cell transplantation treatment.
  4. ECOG body status score 0-2.
  5. 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%).
  6. Patients who voluntarily participate in the clinical trial, understand the research procedure and can sign the informed consent in writing.

Exclusion Criteria:

  1. Patients who with severe cardiac insufficiency, cardiac ejection fraction EF is less than 60%; or severe arrhythmia, the investigator can not tolerate conditioning chemotherapy;
  2. In patients with severe pulmonary insufficiency (obstructive and / or restrictive ventilation disorders), the researchers evaluated the patients who could not tolerate conditioning chemotherapy;
  3. Patients with severe liver function impairment and liver function indexes (alt, TBIL) more than 3 ULN were evaluated as intolerant of conditioning chemotherapy;
  4. 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;
  5. In patients with severe active infection, the researchers evaluated that they could not tolerate conditioning chemotherapy;
  6. Patients who had allergic reactions or serious adverse reactions in the previous use of pretreatment related drugs could not be included in the study.
  7. Other reasons why the researchers could not be selected.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Modified TBF Conditioning Regimen
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
cytarabine+thiotepa+ fludarabine + busulfan intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease free survival
Time Frame: 2 year
2-year DFS
2 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
incidence of toxic reaction
Time Frame: 2 year
2-year incidence of toxic reaction
2 year
overall survival
Time Frame: 2 year
2-year OS
2 year
umulative incidence of relapse
Time Frame: 2 year
2-year incidence of relapse
2 year
ncidence of acute and or chronic graft verus host disease
Time Frame: 2 year
2-year incidence of cGVHD
2 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital of Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2022

Primary Completion (Anticipated)

September 1, 2024

Study Completion (Anticipated)

September 1, 2025

Study Registration Dates

First Submitted

October 26, 2022

First Submitted That Met QC Criteria

October 26, 2022

First Posted (Actual)

October 28, 2022

Study Record Updates

Last Update Posted (Actual)

October 28, 2022

Last Update Submitted That Met QC Criteria

October 26, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZJU-HSCT-MTBF

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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